COMPOSE DU TYPE HYDRURE DE BORE AVEC MODIFICATION ASYMETRIQUE; PREPARATION ET METHODE POUR OBTENIR UN DERIVE D'ALCOOL OPTIQUEMENT ACTIF GRACE A CE COMPOSE

ASYMMETRICALLY MODIFIED BORON HYDRIDE TYPE COMPOUND, A PRODUCTION METHOD THEREOF, AND A METHOD FOR PRODUCING AN OPTICALLY ACTIVE ALCOHOL DERIVATIVE BY THE USE THEREOF

Abrégé anglais

ABSTRACT OF THE DISCLOSURE:
The present invention relates to an asymmetrically
modified borohydride type compound obtained by reacting
an optically active amino alcohol represented by the
formula,
<IMG>
wherein R1 represents an aryl, alkyl, cycloalkyl or
aralkyl group, R2 represents an aryl, alkyl, aralkyl or
alkoxycarbonyl group, R3 represents a hydrogen atom or an
alkyl or aralkyl group, and a mark * means an asymmetric
carbon, or its salt with an acid with a borohydride
compound; its production method; and a method for producing
an optically active alcohol derivative which is useful as
fungicides, herbicides or plant growth regulators,
represented by the formula,
<IMG>
wherein R4 represents an alkyl, cycloalkyl or cycloalkenyl
group, or a phenyl group which may be substituted with at
least one of halogen, alkyl, haloalkyl, cyano, alkoxyl,
phenoxy or phenyl, R5 represents an imidazol-1-yl or
1,2,4-triazol-1-yl group, R6 represents a tert-butyl group,

or a 1,1-dimethyl-2-phenylethyl group wherein benzene ring
may be substituted with at least one of halogen atom, and
a mark * has the same meaning as above, by carrying out
the asymmetric reduction of a ketone compound represented
by the formula,
<IMG>
wherein R4, R5 and R6 have the same meanings as above, with
said asymmetrically modified boron hydride type compound.

Revendications

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. An asymmetrically modified boron hydride type compound
obtained by reacting an optically active amino alcohol represented by
the formula (I),
(I)
<IMG>
wherein R1 represents an aryl, alkyl, cycloalkyl or aralkyl group, R2
represents an aryl, alkyl, aralkyl or alkoxycarbonyl group, R3
represents a hydrogen atom or an alkyl or aralkyl group, and a mark *
means an asymmetric carbon, or its salt obtained from an acid selected
from the group consisting of mineral acids, carboxylic acids and organic
sulfonic acids with a borane or a metal borohydride, respectively.
2. A compound according to Claim 1, wherein, in the above
formula (I), R1 is a C6-C16 aryl selected for a phenyl group which may
be substituted with a least one of halogen, alkyl, cyano, alkoxy and
alkoxycarbonyl, and a naphthyl group which may be substituted with a
least one of halogen, alkyl, cyano, alkoxyl and alkoxycarbonyl, a C1-C10
alkyl, C5-C10 cycloalkyl or C7-C16 aralkyl group, R2 is a C6-C16 aryl,
C1-C10 alkyl or C7-C16 aralkyl group or an alkyloxycarbonyl group in
which the number of carbon atoms constituting the alkyl group is 1 to
10, and R3 is a hydrogen atom.
3. A compound according to Claim 1, where, in the above formula
(I), R1 is a phenyl group which may be substituted with at least one of
halogen, alkyl, cyano, alkoxy or alkoxycarbonyl, or a naphthyl group
which may be substituted with at least one of halogen, alkyl, cyano,
alkoxyl or alkoxycarbonyl, R2 is a C1-C5 alkyl group, and
57

R3 is a hydrogen atom.
4. A compound according to Claim 1, wherein, in the
above formula (I), R1 is a naphthyl group, R2 is a methyl
group and R3 is a hydrogen atom.
5. A compound according to Claim 1, wherein, in the
above formula (I), R1 is a 2,5-dimethylphenyl group, R2 is
a methyl group and R3 is a hydrogen atom.
6. A compound according to Claim 1, wherein, in the
above formula (I), R1 is a phenyl group, R2 is a methyl
group and R3 is a hydrogen atom.
7. A compound according to Claim 1, wherein the
borohydride compound is a metal borohydride.
8. A compound according to Claim 7, wherein the
metal borohydride is sodium borohydride, potassium boro-
hydride, lithium borohydride or zinc borohydride.
9. A compound according to Claim 7, wherein the
molar ratio of the salt of the optically active amino
alcohol to the metal borohydride is 1 : 0.7 to 1 : 1.3, as
converted to boron basis.
10. A compound according to Claim 1, wherein
the borohydride compound is a borane.
11. A compound according to Claim 10, wherein the
molar ratio of the optically active amino alcohol to the
borane is 1 : 0.7 to 1 : 1.3, as converted to boron basis.
12. A method for producing an asymmetrically modified
borohydride type compound characterized in that an optically
active amino alcohol represented by the formula (I),
58

<IMG> (I)
wherein R1 represents an aryl, alkyl, cycloalkyl or aralkyl group, R2
represents an aryl, alkyl, aralkyl or alkoxycarbonyl group, R3
represents a hydrogen atom or a C1-C6 alkyl or aralkyl group, and a mark
* means an asymmetric carbon, or its salt obtained from an acid selected
from the group consisting of mineral acids, carboxylic acids and organic
sulfonic acids is reacted with a borane or a metal borohydride,
respectively.
13. A method according to Claim 12, wherein, in the above
formula (I), R1 is a C6-C16 aryl, selected from a phenyl group which may
be substituted with a least one of halogen, alkyl, cyano, alkoxy and
alkoxycarbonyl, and a naphthyl group which may be substituted with at
least one of halogen, alkyl, cyano, alkoxyl and alkoxycarbonyl, C1-C10
alkyl, C5-C10 cycloalkyl or C7-C16 aralkyl group, R2 is a C6-C16 aryl,
C1-C10 alkyl or C7-C16 aralkyl group or an alkyloxycarbonyl group in
which the number of carbon atoms constituting the alkyl group is 1 to
10, and R3 is a hydrogen atom.
14. A method according to Claim 12, wherein, in the above
formula (I), R1 is a phenyl group which may be substituted with at least
one of halogen, alkyl, cyano, alkoxy or alkoxycarbonyl, or a naphthyl
group which may be substituted with a least one of halogen, alkyl,
cyano, alkoxyl or alkoxycarbonyl, R2 is a C1-C5 alkyl group, and R3 is a
hydrogen atom.
15. A method according to Claim 12, wherein, in the above
formula (I), R1 is a naphthyl group, R2 is a methyl group and R3 is a
hydrogen atom.
16. A method according to Claim 12, wherein, in the
59

above formula (I), R1 is a 2,5-dimethylphenyl group, R2 is
a methyl group and R3 is a hydrogen atom.
17. A method according to Claim 12, wherein, in the
above formula (I), R1 is a phenyl group, R2 is a methyl
group and R3 is a hydrogen atom.
18. A method according to Claim 12 , wherein the
borohydride compound is a metal borohydride.
19. A method according to Claim 18, wherein the metal
borohydride is sodium borohydride, potassium borohydride,
lithium borohydride or zinc borohydride.
20. A method according to Claim 18, wherein the molar
ratio of the salt of the optically active amino alcohol to
the metal borohydride is 1 : 0.7 to 1 : 1.3, as converted
to boron basis.
21. A method according to Claim 12 , wherein the
borohydride compound is a borane.
22. A method according to Claim 21, wherein the molar
ratio of the optically active amino alcohol to the borane
is 1 : 0.7 to 1 : 1.3, as converted to boron basis.
23. A method for producing an optically active
alcohol derivative represented by the formula (III),
<IMG> (III)
wherein R4 represents an alkyl, cycloalkyl or cycloalkenyl
group, or a phenyl group which may be substituted with at

least one of halogen, alkyl, haloalkyl, cyano, alkoxyl, phenoxy
or phenyl, R5 represents a 1,2,4-triazol-l-yl group, R6 repre-
sents a tert-butyl group, or a 1,1-dimethyl-2-phenylethyl group
wherein benzene ring may be substituted with at least one of
halogen atom, and a mark * has the same meaning as above, charac-
terized in that the asymmetric reduction of a ketone compound
represented by the formula (II),
<IMG> (II)
wherein R4, R5 and R6 have the same meanings as above, is carried
out in the presence or absence of an acid with an asymmetrically
modified borohydride type compound obtained by reacting an opti-
cally active amino alcohol represented by the formula (I),
<IMG> (I)
wherein R1 represents an aryl, alkyl, cycloalkyl or aralkyl
group, R2 represents an aryl, alkyl, aralkyl or alkoxy-carbonyl
group, R3 represents a hydrogen atom of a C1-C6 alkyl or aralkyl
group, and a mark * has the same meaning as above or its salt
obtained from an acid selected from the group consisting of
mineral acids, carboxylic acids and organic sulfonic acids with a
borane or metal borohydride, respectively.
24. A method according to claim 23, wherein in the
above formulae (II) and (III), R4 is a C1-C10 alkyl, C6-C10
cycloalkyl or C6-C10 cycloalkenyl group or a phenyl
61

group which may be substituted with at least one of halogen,
C1-C10 alkyl, C1-C10 haloalkyl, cyano, C1-C10 alkoxyl,
phenoxy or phenyl.
25. A method according to Claim 23, wherein, in the
above formulae (II) and (III), R4 is a 2,4-dichlorophenyl
group, R5 is a 1,2,4-triazol-l-yl group and R6 is a tert-
butyl group.
26. A method according to Claim 23, wherein, in the
above formulae (II) and (III), R4 is a 4-chlorophenyl group,
R5 is a 1,2,4-triazol-l-yl group and R6 is a tert-butyl
group.
27. A method according to Claim 23, wherein, in the
above formulae (II) and (III), R4 is a cyclohexyl group, R5
is a 1,2,4-triazol-l-yl group and R6 is a tert-butyl group.
28. A method according to Claim 23, wherein, in the
above formula (I), R1 is a C6-C16 aryl, C1-C10 alkyl,
C5-C10 cycloalkyl or C7-C16 aralkyl group, R2 is a C6-C16
aryl, C1-C10 alkyl or C7-C16 aralkyl group or an alkyloxy-
carbonyl group in which the number of carbon atoms constitut-
ing the alkyl group is 1 to 10, and R3 is a hydrogen atom.
29. A method according to Claim 23, wherein, in the
above formula (I), R1 is a phenyl group which may be
substituted with at least one of halogen, alkyl, cyano,
alkoxy or alkoxycarbonyl, or a naphthyl group which may be
substituted with at least one of halogen, alkyl, cyano,
alkoxyl or alkoxycarbonyl, R2 is a lower alkyl group, and
R3 is a hydrogen atom.
30. A method according to Claim 23, wherein, in the
62

above formula (I), R1 is a naphthyl group, R2 is a methyl
group and R3 is a hydrogen atom.
31. A method according to Claim 23, wherein, in the
above formula (I), R1 is a 2,5-dimethylphenyl group, R2 is
a methyl group and R3 is a hydrogen atom.
32. A method according to Claim 23, wherein, in the
above formula (I), R1 is a phenyl group, R2 is a methyl
group and R3 is a hydrogen atom.
33. A method according to Claim 23 , wherein the
borohydride compound is a metal borohydride.
34. A method according to Claim 33, wherein the metal
borohydride is sodium borohydride, potassium borohydride,
lithium borohydride or zinc borohydride.
35. A method according to Claim 33, wherein the
molar ratio of the salt of the optically active amino
alcohol to the metal borohydride is 1 : 0.7 to 1 : 1.3, as
converted to boron basis.
36. A method according to Claim 23 , wherein
the borohydride compound is a borane.
37. A method according to Claim 36, wherein the molar
ratio of the optically active amino alcohol to the borane
is 1 : 0.7 to 1 : 1.3, as converted to boron basis.
38. A method according to Claim 33, wherein the
asymmetric reduction is carried out in the presence of an
acid.
39. A method according to Claim 38, wherein the acid
is Lewis acids, organic acids or mineral acids.
63

CLAIMS SUPPORTED BY THE SUPPLEMENTARY DISCLOSURE
40. A compound according to claim 1, wherein, in
the above formula (I), R1 is a 2,4-dimethoxyphenyl group,
R2 is a methyl group and R3 is a hydrogen atom.
41. A compound according to claim 1, wherein, in
the above formula (I), R1 is a 2,5-diethoxyphenyl group, R2
is a methyl group and R3 is a hydrogen atom.
42. A compound according to claim 1, wherein, in
-the above formula (I), R1 is a 2,5-dimethoxyphenyl group, R2
is a methyl group and R3 is a hydrogen atom.
43. A compound according to claim 1, wherein, in
the above formula (I), R1 is a 2-methoxyphenyl group, R2
is a methyl group and R3 is a hydrogen atom.
44. A method according to claim 12, wherein, in
the above formula (I), R1 is a 2,4-dimethoxyphenyl group,
R2 is a methyl group and R3 is a hydrogen atom.
45. A method according to claim 12, wherein, in
the above formula (I), R1 is a 2,5-diethoxyphenyl group,
R2 is a methyl group and R3 is a hydrogen atom.
46. A method according to claim 12, wherein, in
the above formula (I), R1 is a 2,5-dimethoxyphenyl group,
R2 is a ethyl group and R3 is a hydrogen atom.
47. A method according to claim 12, wherein, in
the above formula (I), R1 is a 2-methoxyphenyl group, R2 is
a methyl group and R3 is a hydrogen atom.
48. A method according to claim 23, wherein, in
the above formula (I), R1 is a 2,4-dimethoxyphenyl group,
R2 is a methyl group and R3 is a hydrogen atom.
64

49. A method according to claim 23, wherein, in
the above formula (I), R1 is a 2,5-diethoxyphenyl group,
R2 is a methyl group and R3 is a hydrogen atom.
50. A method according to claim 23, wherein, in
the above formula (I), R1 is a 2,5-dimethoxyphenyl group,
R2 is an ethyl group and R3 is a hydrogen atom.
51. A method according to claim 23, wherein, in
the above formula (I), R1 is a 2-methoxyphenyl group, R2
is a methyl group and R3 is a hydrogen atom.
52. A compound according to claim 1, wherein, in
the above formula (I), R1 is a 2-ethoxyphenyl group, R2
is a methyl group and R3 is a hydrogen atom.
53. A method according to claim 12, wherein, in
the above formula (I), R1 is a 2-ethoxyphenyl group, R2 is
a methyl group and R3 is a hydrogen atom.
54. A method according to claim 23, wherein, in
the above formula (I), R1 is a 2-ethoxyphenyl group, R2 is a
methyl group and R3 is a hydrogen atom.

Description

g7
1 The present invention relates to a novel
asymmetrically modified boron hydride type compound, its
production and a method for producing an optically active
alcohol derivative using the compound. More particularly,
it relates to an asymmetrically modified boron hydride type
compound obtained by reacting an optically active amino
alcohol represented by the formula (I),
* *
R - CH - CH - R~
1 1 1 ,. (I)
OH NHR3
wherein Rl represents an aryl, alkyl, cycloalkyl or aralkyl
group, R2 represents an aryl, alkyl, aralkyl or alkoxy-
carbonyl group, R3 represents a hydrogen atom or an alkylor aralkyl group, and a mark * means an asymmetric carbon,
or its salt with an acid, with a boron hydride compound; its
production method; and a method for producing an optically
active alcohol derivative represented by the formula (III),
OH
R -CH = C - CH - R6 (III)
R5
wherein R4 represents an alkyl, cycloalkyl or cycloalkenyl
group, or a phenyl group which may be substituted with at

~Z2~9~
1 least one of halogen, alkyl, haloalkyl, cyano, alkoxyl,
phenoxy or phenyl, R5 represents an imidazol-l-yl or
1,2,4-triazol-1-yl group, R6 represents a tert-butyl group,
or a l,l-dimethyl-2-phenylethyl group wherein benzene
ring may be substituted with at least one of halogen atom,
and a mark * has the same meaning as above, by carrying out
the asymmetric reduction of a ketone compound represented by
the formula (II),
R4 - CH = C - C - R6 (II)
R5
wherein R4, R5 and R6 have the same meanings as above, with
said asymmetrically modified boron hydride type compound.
The alcohol derivative represented by the above
formula (III), i.e. an azole type ~ unsaturated alcohol
derivative is known to be useful as an active ingredient for
fungicides, plant growth regulators or herbicides, as
represented for example by 1-(2,4-dichlorophenyl)-2-(1,2,4-
triazol-l-yl)-4,4-dimethyl-1-penten-3-ol, 1-(4-chloro-
phenyl)-2-(1,2,4-triazol-1-yl)-4,4-dimethyl-1-penten-3-ol
and l-cyclohexyl-2-(1,2,4-triazol-1-yl)-4,4-dimethyl-1-
penten-3-ol [Japanese Patent Application Kokai (Laid-open)
u~ . ~ 0~ ~s"
Nos. 124,771/1980, 10054~/1979 and 111,477/1980]. And, it is
also well known that there is a remarkable difference in the
activity between the optical isomers, and that, for
example, with reference to the foregoing 1-~2,4

)97
1 dichlorophenyl)-2~(1,2,4 triazol-1-yl)-4,4-dimethyl-l-
penten-3-ol and 1-(4-chlorophenyl)-2-~1,2,4-triazol-l-yl)-
4,4-dimethyl-1-penten-3-ol, the (-)-isomer has a strong
activity as fungicides, while the (+)-isomer has a strong
activity as plant growth regulators and herbicides [Japanese
~ Q,l d
~,' Patent Application Kokai (~ -open) Nos. 99575/1982 and
106669/1982].
For this reason, there is a great demand for the
development of a method to produce either one of the (-)-
or (+)-optical isomer according to intended uses and yet
with a good efflciency in industry.
As the conventionally well-known common reducing
agent for reducing the carbonyl group of ketone compounds
into alcohol compounds, there are various reagents
represented by lithium aluminum hydride and sodium boro-
hydride. -The reduction product produced when these reagents
are used is an optically inactive, i.e. racemic compound,
and when these reagents are used for the reduction of
ketone compounds having an unsaturated bond, particularly
~ conjugated unsaturated ketones like the material used
in the method of the present invention, reduction of the
double bond in addition to the carbonyl group is easy to
occur, and besides there also comes out a possibility that
the steric configuration correlated with the double bond is
isomerized.
C~h l/e,n~o>q~
As the ~e=~e~ r~f employed method for
'~ ~ producing optically active alcohol derivatives by asymmetric
reduction, there are the following methods to carry out
-- 3 --

~Z;~i()97
1 the asymmetric reduction of ketone compounds with lithium
aluminum hydride modified with an optically active compound:
A method of using an optically active N-methylephedrine
[I. Jacquet, et al., Tetrahedron Letters, 1974, 2065; J.P.
Vigneron, et al., Tetrahedron, 32, 939 (1976); J.P.
Vigneron, et al., Tetrahedron Letters, 1979, 2683; idem,
ibid., 1980, 1735; and Japanese Patent Application Kokai
(Laid-open) Nos. 99575/1982 and 106669/1982]; a method of
using an optically active proline derivative [M. Asami,
et al., Heterocycles, 12, 499 (1979)] and a method of using
an optically active binaphthyl derivative [R. Noyori, et al.,
J. Am. Chem. Soc., 101, 3129 (1979); R. Noyori, et al.,
ibid., 101, 5843 (1979)].
These methods, however, may not always be said to
be satisfactory in industry, for example, in the following
points: (1) Since lithium aluminum hydride is used, there
is a danger such as ignition by contact with moisture, and
(2) in order to obtain an alcohol compound having a higher
optical purity~ additives such as N-substituted aniline are
required in large amounts.
Also, in asymmetric reduction, the following
methods are reported as a method for producing optically
active alcohols using an asymmetrically modified boron
hydride-reducing agent:
~ A method of using sodium borohydride and the onium
salt of optically active ephedrine [described in S.
Colona, et al., J. Chem. Soc., Perkin Trans I, 371
(1978)],
-- 4

~2~ 9~
1 ~ a method of using an optically active amine-borane
complex [described in R.F. Borch, et al., J. Org.
Chem. 37, 2347 (1972~],
~ a method of using an ~-amino acid ester-borane complex
[described in M.F. Grundon, et al., Tetrahedron
Letters, 295 (1976)], and
a method of the asymmetric reduction of aromatic ketones
with an optically active amino alcohol and borane
~described in A. Hirao, et al., J. Chem. Soc., Chem.
Comm., 315 (1981); S. Itsuno, et al., ibid., 469
(1983); and S. Itsuno, et al., J. Chem. Soc. Perkin
Trans I, 1673 (1983)].
But, the methods ~ , ~ and ~ are too low in
optical yield to say that they are a practical method.
Also, the method ~ may not always be said to be
satisfactory to carry it out in industry because, in order
to attain high optical purity t borane of two times by mole,
as converted to boron basis, as much as amino alcohol is
required.
In view of the situation like this, the present
inventors extensively studied a method for obtaining the
optically active alcohol derivative represented by the
formula (III) by the asymmetric reduction of the ketone
compound represented by the above formula (II), and as a
result, found that, by using an asymmetrically modified
boron hydride compound (hereinafter referred to as
present compound) obtained by reacting the optically active
amino alcohol represented by the above formula (I) or its

~Zl~g7
1 salt with an acid ~ith a boron hydrlde compound, only the
carbonyl group is selectively reduced into the objective
optically active alcohol derivative with safety as well as
good efficiency.
Next, the present invention will be illustrated.
In the optically active amino alcohol represented
by the above ~ormula (I), a material for the present
compound, specific examples of a substituent Rl include a
Cl-C10 alkyl, C5-C10 cycloalkyl and C7-C16 aralkyl groups,
a phenyl group which may be substituted with at least one
of halogen, alkyl, cyano, alkoxyl or alkoxycarbonyl, and a
naphthyl group which may be substituted with at least one
of halogen, alkyl, cyano, alkoxyl or alkoxycarbonyl.
Specific examples of R2 include a C6-C16 aryl, Cl-C10 alkyl
and C7-C16 aralkyl groups and an alkyloxycarbonyl group in
which the number of carbon atoms constituting the alkyl
group is 1 to 10. Specific examples of R3 include a
hydrogen atom, a Cl-C6 alkyl and C7-C16 aralkyl groups.
More specifically, as the optically active amino alcohol
represented by the formula (I), there may be given
norephedrine, norpseudoephedrine, threonine ester, 1,2-
diphenyl-2-amino-1-ethanol, 1~(2,5-dimethylphenyl)-2-amino-1-
propanol and l-~-naphthyl-2-amino-1-propanol. These optical-
ly active amino alcohols are produced, for example, by the
methods described in M.J. Kalm, J. Org. Chem., 25, 1929-37
(1960); W.H. Hartung, et al., J. Am. Chem. Soc., 52, 3317-22
(1930); W.H. Hartung, et al., J. Am. Chem. Soc., 51,
2262-6 (1929); M.C. Kloetzel, et al., J. Org. Chem., 11,

12~ 7
1 390-4 (1946), and the like.
In the present invention, the halogen atom
represents fluorine atom, chlorine atom or bromine atom.
Next, reference will be made to a method for
producing the present compound.
The present compound, when the boron hydride
compound is a metal borohydride, is obtained by reacting
a salt, as obtained from the optically active amino alcohol
represented by the formula (I) and an acid, with the metal
borohydride in a solvent, or when the borohydride compound
is a borane, it is obtained by directly reacting the
optically active amino alcohol represented by the formula
(I) with the borane in a solvent. As the foregoing acid
which is a material for producing the salt of the optically
active amino alcohol, there are given mineral acids (e.g.
hydrochloric acid, sulfuric acid, nitric acid, phosphoric
acid, carboxylic acids (e.g. acetic acid), organic sulfonic
acids (e.g. p-toluenesulfonic acid) and the like. Said
salt may be used as such or may be produced, in situ, from
the optically active amino alcohol and the acid in the
reaction system for producing the present reducing agent.
As the metal borohydride described above, there
are given for example sodium borohydride, potassium boro-
hydride, lithium borohydride, zinc borohydride, etc.
Generally, however, the object of the present invention can
sufficiently be achieved by using easily available sodium
borohydride. As the borane, for example diborane, borane-
tetrahydrofuran complex, borane-dimethyl sulfide complex,

~2~9~
1 etc. may be given.
In production of the present compound, the molar
ratio of the borohydride compouncl to the optically active
amino alcohol is, when said compound is a metal borohydride,
0.7 : 1 to 2 : 1, preferably 0.7 : 1 to 1.3 : 1, more
preferably 1 to 1, as converted to boron basis, and when
said compound is a borane, said molar ratio is 0.7 : 1 to
1.3 : 1, preferably 1 to 1.
The solvent used in producing the present compound
is not particularly limited, so long as it does not take
part in the reaction. For example, however, there are
given aromatic hydrocarbons (e.g. benzene, toluene, xylene,
chlorobenzene), halogenated hydrocarbons (e.g. methylene
chloride, 1,2-dichloroethane, chloroform, carbon tetra-
chloride~, and mixtures thereof. When the metal borohydrideis used, in order to solve it, for example dimethyl
sulfoxide, diglyme, dimethylformamide, 1,3-dimethyl-2-
imidazolidinone or the like may be used in combination.
The reaction temperature is generally within a range of
-78 to 100C, preferably -40 to 100C. The reaction is
generally carried out in an inert gas atmosphere such as
nitrogen, argon, etc.
Also, by decomposing the present compound with
an aqueous alkali solution, a compound represented by the
formula (V),

)g7
* *
R - CH - CH - R2 (V)
1 wherein Rl, R2, R3 and a mark * have the same meanings as
above, is obtained.
The present compound thus obtained may be used for
the subsequent reduction after separated from the reaction
solution, but generally, it is used as the solution without
being separated therefrom.
Next, re~erence will be made to a method for
producing the optically active alcohol derivative of the
above formula tIII) by reduction of the ketone compound
represented by the above formula (II) using the present
compound thus obtained.
The amount of the present -compound used in the
reduction is not less than 0.5 mole, generally within a
range of 1 to 5 moles, as converted to boron basis, based
on 1 mole of the ketone compound represented by the formula
(II), and even the range of 1 to 2 moles can sufficiently
achieve the object.
Also, the solvent used in the foregoing reduction
is not particularly limited, so long as it is an inactive
solvent. Preferably, however, organic solvents such as
aromatic hydrocarhons (e.g. benzene, toluene, xylene,
chlorobenzene), halogenated hydrocarbons (e.g. methylene
chloride, ~,2-dichloroethane, chloroform, carbon

:~2:~9'~
1 tetrachloride), ethers ~e.g. diethyl ether, tetrahydrofuran,
dioxane, diglyme) and mi~tures thereof are used. Also,
the solvent used in producing the present compound may be
used as it is or in mixture with the solvents described
above. The reduction is generally carried out in an inert
gas atmosphere as described above. The temperature of
the reduction is generally within a range of -30 to 100C,
and industrially within a range of -10 to 50C.
The foregoing reduction may be carried out in the
presence of an acid, and particularly when sodium boro-
hydride is used as a material for the present compound,
isomerization between the E form and Z form of the ketone
compound represented by the above formula (I) is inhibited,
whereby the yield of the objective optically active alcohol
derivative can be increased. As the acid, there are given
for example Iewis acids (e.g. titanium tetrachloride, boron
trifluoride etherate, aluminum chloride), carboxylic acids
(e.g. acetic acid, chloroacetic acid, propionic acid) and
mineral acids ~e.g. hydrochloric acid, sulfuric acid,
phosphoric acid). The molar ratio of these acids to the
ketone compound is generally within a range of 0.01 : 1 to
1 : 1, preferably 0.01 : 1 to 0.5 : 1.
After the reduction is carried out in this way,
the aqueous solution of a mineral acid (e.g. hydrochloric
acid, sulfuric acid) is generally added to the reaction
solution, the organic layer is separated from the aqueous
layer, washed with water and dried, and then the organic
solvent is removed by evaporation. By this procedure, the
-- 10 --

(J 97
1 objective aforementioned optically active alcohol deri~ative
represented by the formula (III) is obtained in a high
yield.
The optical purity is obtained by measuring the
optical rotation of the product obtained, or directly
measuring the enantiomer ratio by high performance liquid
chromatography with optically active packing materials.
Hereupon, the optically active amino alcohol used
can easily be recovered, with its steric configuration
maintained, by adding an aqueous alkali solution to the
aqueous layer after the reaction and extracting with an
organic solvent. The recovered optically active amino
alcohol can be re-used.
Example 1
In a nitrogen atmosphere, 0.338 g of (+)-
norephedrine hydrochloride was suspended in 5 ml of deutero
chloroform, and after cooling to -30C, a solution of
0.0681 g of sodium borohydride in 1 ml of dimethylformamide
was added. On raising the temperature of the resulting
20 mixture from -30C to room temperature over 2 hours, 87 ml
of hydrogen gas was generated to obtain a solution of the
present compound. llB nuclear magnetic resonance spectrum
(standard, BF3~OEt2) of this solution was as follows:
-20.95 ppm, +7.21 ppm.
Thereafter, this solution was de~omposed with
2.5N aqueous sodium hydroxide solution, and the organic
layer was washed with water and purified by column

U97
1 chromatography on silica gel with a n-hexane/ethyl acetate
(1 : l) mixture as a developing solvent to obtain 0.112 g
of a crystal.
llB nuclear magnetic resonance spectrum (standard,
BF3~OEt2): -20-5 ppm
m.p. 93 -95C (dec.)
This crystal, as a result of X-ray diffraction
analysis, was identified to be a borohydride compound
having the following structure:
CH - CH - CH3 [~]D + 49 7 (c - 1.0, THF)
OH N-~BH3
Example 2
~ eaction was carried out in the same manner as in
Example l except that dimethylformamide was replaced by
deutero dimethylformamide, to obtain a solution of the
present compound having the following physical property:
H nuclear magnetic resonance spectrum [CDCl3-DMF-d7,
~(ppm)]: 0.97(d), 1.04(d), 2.75-3.15(m), 3.1-3.5(broad),
4~2-4.7(broad), 5.18(d), 7.31(s)
Examples 3 and 4
Reaction was carried out in the same manner as in
Example 2 except that (+)-norephedrine hydrochloride was
replaced by (+)-l-(2,5-dimethylphenyl)-2-amino-l-propanol
hydrochloride and (-)-l-~-naphthyl-2-amino-l-propanol

~L~Z2~ 7
1 hydrochloride, to obtain a solution of the present compound
having the physlcal property shown in Table 1.
Table
Example No. llB NMR spectrum [~(ppm)]
_
3 -20.6, +6.5
4 -20.3, +6.4
Example 5
In a nitrogen atmosphere, a solution of 0.272 g
(1.8 mmoles) of (+)-norephedrine in 4 ml of 1,2-dichloro-
ethane was added dropwise at -78C to a solution comprising
1.8 ml (0.9 mmole) of a 0.50M diborane-tetrahydrofuran
solution and 2 ml of 1,2-dichloroethane, and the tempera-
ture of the resulting mixture was raised from -78C to room
temperature over about 2 hours. 11B nuclear magnetic
resonance spectrum of this solution was as follows: -20.7
ppm, +7.7 ppm.
Example 6
In a nitrogen atmosphere, 0.338 g (1.8 mmoles) of
(+)-norephedrine hydrochloride was suspended in 5 ml of
1,2-dichloroethane, and after cooling to -30~C, a solution
of 0.0681 g (1.8 mmoles) of sodium borohydride in 1 ml
of dimethylformamide was added. On raising the temperature
of the resulting suspension from -30C to room temperature

~Z~ '7
1 over 2 hours, 87 ml of hydrogen gas was generated. There-
after, a solution of 0.39 g ~1.2 mmoles~ of (E)-1-(2,4-
dichlorophenyl)-2-(1,2,4-triazol-1-yl)-4,4-dimethyl-1-
penten-3-one (E/Z=99.9/0.1) in 4 ml of 1,2-dichloroethane
was added to this suspension at room temperature, and then
stirring was carried out for 23 hours. Thereafter, 6 ml of
2M hydrochloric acid was added, followed by stirring for
2 hours. The organic layer was washed with water, dried
and concentrated under reduced pressure. The residue was
purified on a column packed with 2 g of silica gel with
a chloroform solvent and then concentrated under reduced
pressure to obtain 0.39 g of (-)-(E)-1-(2,4-dichlorophenyl)-
2-(1,2,4-triazol-1-yl)-4,4-dimethyl-1-penten-3-ol as a
crude crystal. By gas-chromatographic analysis, it was found
that the conversion was 96.4%, and the composition of the
reaction product was: E-form alcohol, 98.3% and Z-form
alcohol, 1.7% (Z-form alcohol was produced through
isomerization of the ketone compound to the Z-form, followed
by reduction of the carbonyl group).
Optical rotation [~]D -19.93 (c=1.0, CHC13)
~y high-performance liquid-chromatographic
analysis using an optically active column, it was found
that the enantiomer ratio of the E-form alcohol was:
(-)-isomer, 85.1% and (+)-isomer, 14.9%. The optical yield
25 was 70.2%.
Examples 7 to 10
Reaction was carried out according to Example 6
- 14 -

12Z~97
1 using the reactlon solvents described below in place of 1,2-
dichloroethane, to obtain (-)-(E)-1-(2,4-dichlorophenyl)-
2~ 2,4-triazol-1-yl)-4,4-dimethyl-1-penten-3-ol.
The results are shown in Table 2. In the table,
the solvents in parentheses in the column, "Reaction
solvent", are a solvent used for dissolving sodium boro-
hydride.
- 15 -

vs7
~o~ ~ o ~ ~
-
+ e . In u~
O I O ~ ~D O ~ C~
~ ~l ~ ~
1 0 Il~ O ~ In
. oo ~
~ ~ o
1~' 10~ co, _ c~
k,~ ~ o ~ a~
O ~ t) --
~ I ~
O ~ O
O ~0 d~ 00 O Ct~
~ ~ ~ -- CO I~ ~D t`
~ ~ ~ ~ cn a~ a~
a~ _ _
E~ ~ ~ I_ ~r
~3 a ~ ~
_
~,
~ In ~ ll~ N
~a o ~3 s t~ ~r t`l 1_
p:;- O --
_ _ .
l l ~
~, s-, a)
O ~ O O_ ~ _ N I _
~1 ~ ~a) s~ ~:>~, ~ o ~ ~
~ ~ ~ e ~, ~ rl ~ s rl R S ,l
c~ ~ ~ .,~ ~ ~ X ~ ~ 6 O ~ E~
a ~ -I ~ ~ a) o a~ s~
~ OI ~ ~ I td ~ ~ 6 6 0 6
P~~ .C ~1 ~ s ,~ ~ ~ ~1 ~ ~ ~ ~
o ~ o s ~ o
-- ~ a~--~Q E~--~
. __
6~; r~ co ~ ~
X _ _
-- 16 --

~L2ZlV~
l Examples 11 to 13
Reaction was carried out according to Example 6
using (E)-1-(4-chlorophenyl)-2-(1,2,4-triazol-l-yl)-4,4-
dimethyl-l-penten-3-one (E/Z=99.8/0.2) in place of (E)-
l-(2,4-dichlorophenyl-2-(1,2,4-triazol-l-yl)-4,4-dimethyl-
l-penten-3-one and at varying molar ratlos, 1.0, l.l and
1.2, of sodium borohydride to norephedrine hydrochloride.
The results are shown in Table 3. Hereupon the saturated
alcohol of the reaction products means a product obtained by
hydrogenation of both the carbonyl group and the carbon/
carbon double bond contained in the ketone compound which is
a material.
- 17 -

:~2Z1~)97
_ ~ _ .
~,C ~ ~ o
r1 ~ O O o\ ~ ~r I`
a~ ~D
.," ~
O~ .
+ ~ ~ I_ U~
o, o ~ ~ ~
~3~,
~ ~o ~ ~ ~
_ ~o . . _
oo ~o Lr) ~ ~
~_
q~ ~ 0 o ~
.~ ~ ~ _ __
~,C I~ ~. ~
0 3 ~0 . .
_ . r~ r
E~ au ^ u~ a~ 1~
~ ~ ~P r~ G~ ~D
,0-~ _ _ ~ _
I ~ o ~ u~
,~, e _ ~r ~ u~
~ _
o .~
0~ o ~1 ~
h O~1 3 0 S~ . .
~ o _, _,
o~ --~
~Z ~ ~1
- - --
-- 18 --

~22~ 97
1 Examples 14 and 15
In a nitrogen atmosphere, a solution of 1.8 mmoles
of the following each acid in 1 ml of 1,2-dichloroethane
was added to a solution of 0.272 g (1.8 mmoles) of (+)-
norephedrine in 4 ml of 1,2-dichloroethane, and after
cooling to -30C, a solution of 0.0681 g (1.8 mmoles) of
sodium borohydride in 1 ml of dimethylformamide was added.
The temperature of the resulting mixture was raised from
-30C to room temperature over 2 hours to prepare the present
compound. Thereafter, asymmetric reduction of the ketone
compound was carried out in the same manner as in Example 6.
The results are shown in Table 4.
-- 19 --

~2~
. ,.. . _ . .. ..
L ~
U ~ s, ~: ^ ~ ~
~1 ~ o o dP ~9 ~r
a) ~ t~ -~
Q~
o ~ ~ I
,~ _ L
O I o~l n co
o I
~rl W O
. r~
~I
~0
~.~C U~
LO O ~ o U~
1:5 N (~
O ~'C5So~ O l
~ ~ ~ A
~r rl U~
~0
a) s~ u~ I_
O O d~ .
E~ ~ ~o ~r
~ CO a~
o~ ~ _J
~C,) U~
_
~ 'U
'~
~: U
o ~ o
Z Ln
W
-- 20 --

~2~U9~
1 Example 16
Reaction was carried out on a scale of ten times
that of Example 6. ~n a nitrogen atmosphere, a solution of
0.681 g (0.018 mole) of sodium borohydride in 9.44 g of
dimethylformamide was added dropwise at -20C to a suspension
of 3.38 g (0.018 mole) of (+)-norephedrine hydrochloride in
62.8 g of 1,2-dichloroethane, and the temperature of the
resulting mixture was raised from -20~C to room temperature
over 2 hours. Thereafter, a solution of 3.89 g (0.012
mole) of (E)-1-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-yl)-
4,4-dimethyl-1-penten-3-one (E/Z=97.6/2.4) in 50.24 g of
1,2-dichloroethane was added, and stirring was carried out
at room temperature for 21 hours and then at 40C for
3 hours. The reaction solution was decomposed with
addition of 7.22 g of 10% hydrochloric acid and 2.1 g of
water, and the organic layer was separated, washed with
water and concentrated under reduced pressure to obtain
3.89 ~ of (-) (E)-1-(2,4-dichlorophenyl)-2-(1,2,4-triazol-
l-yl)-4,4-dimethyl-1-penten-3-ol as a crystal. The conver-
sion of 99.9%, and the composition of the product obtainedwas: E-form alcohol, 95.8%; saturated alcohol, 0.2%;
Z-form alcohol, 3.5%; and others, 0.5%. The enantiomer
ratio of the E-form alcohol was: (-)-isomer, 85.2% and
(+)-isomer, 14.8%. The optical yield was 70.4%.
Example 17
Reaction was carried out in the same manner as
in Example 16 except that the amounts of 1,2-dichloroethanep
- 21 -

~z~1~9~
1 a solvent, used were reduced to 13.52 g and 12.2 g from
62.8 g and 50.24 g, respectively. The conversion was 99.9%,
and the composition of the product obtained was: E-form
alcohol, 88.9%; saturated alcohol, 0.9%; Z-form alcohol,
9.4%; and others, 0.8%. The enantiomer ratio of the E-form
alcohol was: (-)-isomer, 84.1% and (+)-isomer, 15.9%. The
optical yield was 68.2%.
Examples 18 to 24
Asymmetric reduction of each of (E)-l-(Z,4-
dichlorophenyl)-2-(1,2,4-triazol-1-yl)-4,4-dimethyl-1-
penten-3-one (E/Z=97.6/2.4) and (E)-1-(4-chlorophenyl)-
2-(1,2,4-triazol-1-yl~-4,4-dimethyl-1-penten-3-one (E/Z=
98.9/1.1) was carried out according to Example 6 using
the hydrochloride of each optically active amino alcohol
described below in place of (+)-norephedrine hydrochloride.
The results are shown in Table 5.
- 22 -

:~2~9t7
a e ~ ~ ~
~ _ _
-- 23 --

~2~1VC~7
-- - -
- - o, ~~ o
Z~ ~ Z~ N ~
~ *~_O *m_O O *C~_~ *~--æ
o~
-~ J =
,~D"''=
L~_~ L
-- 24 --

097
.~ _. _ . ~
a ~ a~ co O
00~ o~ ~ a~
~, ~ ~
~, ~:~ ~ ~
~ ~ N ~ ~D
-- 25 --

U'~7
_ _ ~
o o o
o U~ U~ ~
o~ ~ ~ oo
o~ r~ ~
o ~ ~ r~
_
o
In ao ~ ~
Q ~ u~ _i a~
E~- _
_
,~ t` ~
~ ~ a~ c~
_ _ __
_ 26 --

~215)97
1 Examples 25 to 29
Reaction was carried out in the same manner as in
Example 6 except that the (E) ancL (Z) forms of l-cyclohexyl-
4,4-dlmethyl-2-(1,2,4-triazol-1-yl)-1-penten-3-one (the
E/Z ratios of the former and the latter were 99.9/0.1 and
0.1/99.9, respectively) were used in place of (E)-l-
(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-yl)-4,4-dimethyl-
l-penten-3-one, and that the hydrochlorides of the optical-
ly active amino alcohols and the solvents (solvents in
parentheses are a solvent used for dissolving sodium
borohydride) described below were used. The results are
shown in Table 6.
- 27 -

o9~
a ___
- D -- ~ o
U l
_ . _
~.~ .~ ~.~
~ O e ~ ~ O e
~ ~ .~ ~ ~ ~
V~ ~, ~ o ~ rl
a ~ o e a
~.~ .,, ~
_ _
s:~ ~ ~ z m_ m~ u--æ~ m_m
E~ ~ 5:_ m ~g--o o--o m_m
~)o ~ ~ ~ ~
o~ l o
_ _ _
O h O O
~ ~V ~ _ ~ _ ~ ~ _
_~ _
O U~ ~D l_ CO
X Z ~ ~ ~
~ _ _ _
-- 28 --

v9 ~
-
~a .
o o
-
a~
o ~
h O
o ~U
_I
a ~ c~
~ ~rl
o
ll
o ~ ~
U 5: t)
C~ ~,
I ~ ~
~D ~ X O
*~--Z
l ~
:: ~
o
E~ ~ O
l o
+
~ o
_
a~
.
-- 29 --

~Z~1~9'7
~P ~ ~ ~ ~U
oo ~ ~ .
~0 ~D W In
~5 ~ , , _
o P~ o~
~o o~ ~ 8 _, ~ 1~ ,
~ ~ ~ o~ ~ ~
o s~ ~ l x r~ O
o
E~ O O o ~ o ,~
~Wo o~ _, ~ __
. . _, o
~ ~ ~ In ao
~ w __~ ~ ~` ~
-- 30 --

~22~)97
~ o
E~ o~
~ 31 --

IU97
1 Example 30
In a nitrogen atmosphere, 0.338 g (1.8 mmoles)
of (+)-norephedrine hydrochloride was suspended in 5 ml of
1,2-dichloroethane, and to this suspension was added at
-30C a solution of 0.0681 g (1.8 mmoles) of sodium boro-
hydride in 1 ml of dimethylformamide. The temperature of
the resulting suspension was raised to room temperature
over 2 hours. Thereafter, to this suspension was added at
room temperature a solution of 0.0108 g (0.18 mmole) of
acetic acid and 0.35 g (1.2 mmoles) of (E)-1-(4-chlorphenyl)-
2-(1,2,4-triazol-1-yl~-4,4-dimethyl-1-penten-3-one (E/Z=
99.8/0.2) in 4 ml of 1,2-dichloroethane. The subsequent
treatment was carried out according to Example 6.
The conversion was 79.4%, and the composition of
the product obtained was: E-form alcohol, 92.5%; saturated
alcohol, 0.3%; and Z-form alcohol, 7.Z~. The enantiomer
ratio of the E-form alcohol was~ isomer, 76.1% and
(+)-isomer, 23.9%. The optical yield was ;2.2%.
Examples 31 to 38
Reaction was carried out according to Example 30
using titanium tetrachloride, boron trifluoride etherate,
monochloroacetic acid, propionic acid and conc. sulfuric
acid in place of acetic acid. The results are shown in
Table 7.
- 32 -

~ZZ1~97
O ~ ~~1 1~r~ ~ ~ N
O o~t~ ~r~i 1~co ~ ~I ~ ~
~ --~OCIDIl~ a~~D CO ~ 0
U
_ _
O
. ~ er ~ ~7 ~r ~ c~
o a) s ~ ~ ~ ~ ~ ~D
~ -
~ ~ _ _
C) 00
O
a) o ~ In
~ ~ ~ .
.,1 ~ ~ ~ f~ O O O O O U~
` a o _ __ ~ __ _ ,1 _
~ ~ I_ ~ ~ ~r~ ~ co ~
~_ ~ o ~ ~ ~ ~ ~ o
~~ o ~O O ~ O O O O O
E~ X~ _ . . . . . . .
~ ~C o O O O o O o O
h 'a t)
~ .~ .~ ~ C~
~ ~ o a) .,, .,,
rl ~ ~ ~ C~ S~
~ ~0 ~ O ~ 4~
u~ ~ ~,1 S~ a~ o .,
.~ ~.C ~ ~ ~ ~ U~
3 ~d,~ ~ t~ S O
a) Z~ ~ :~ s~ ~ .,, .
s~ o a~ o ~a ~ o
~ ~ ~ S ~ rl O ~ .,
,1 0 O ~ O O h O O
~ ~ m a) X ~ _ ~ ~
Q~
~ .
O ~ ~ ~ ~ ~n ~D ~ 0
~ Z ~ ~ ~ ~ ~ ~7 ~ ~
X _ _ __
-- 33 --

v~
- ~o~-c ~v~ ~; ~ - ~ ~ -
o l ~ ~ ~ oo ~ co u~ co co
~ ~ ~ ~ ~ ~ ~ ~ ~r u~
o o ~
- - - - - - -
+ r~ ~ co i~i~ ~ i~ co
a) ~ ~ . . . . . . ~
~ I ~ ~ ~ ~D CO O ~ U~ O
0~ ~ O ~ r~ ~ ~ ,
.
~ O i ~ ~`~CO ~ ~ ~ ~D
8~9 ~D ~ ~i ~ ,~ ~r a~
~0 ~ ~ _ ~ 00 ~ ~D t` i-
~ _ _
~,
~ r~ ~ ~ N If) ~ CO ~I
~` 00 ~7 _ O _1 C~ O ~ ,0~
~ _ __ .
S~ ~5-
Q ~ O ~ _~ ~ ~ ~
. .~ ~0- O
_ _ _
d~
_
,~ U~ ~ In U~ ~ ~1 ~ a~
O O ~o ~ oo _ ~ a~ o a~
1~1 ~ ~ a~ o~ ~ oo ~ co
_ _
-- 34 --

1 Examples 39 to 41
Reaction was carried out according to Example 30
using varying molar ratios of sodium borohydride to
norephedrine hydrochloride. The results are shown in
6 Table 8.
Table 8
Example Molar ratio (%) Molar ratio (%) Re~c- Conver- _
acid to amino borohydride to tlon sion
No. alcohol norephedrine hr (~)
hydrochloride ( ) O
_ _ _
39 15 _ 1.1 24 90.0 _
1.2 43 _ 97.8
41* 15 1.1 24 97.2
_ _ _ _
_
Reaction product Enantiomer Optical
_ ratio (-/+) yield of
E-form Saturated 2-form of E-form E-form
alcohol alcohol alcohol alcohol alcohol
(%) (%) (%) (%)
_
92.1 _ 7.9 79.0/21.0 58.0
_
83.6 0.8 13.4 85.0/15.0 70.0
_
91.2 _ 8.8 75.5/24.5 51.0
_ _
* Chlorobenzene was used in place of 1,2-dichloro-
ethane.
Example 42
In a nitrogen atmosphere, 0.393 g 10.0065 mole)of acetic acid was added to a suspension of 8.18 g

lZ;~ 397
1 (0.0436 mole) of ~ norephedrine hydrochloride in 62.17 g
of chlorobenzene, and then a solution of 1.815 g (0.0480
mole) of sodium borohydride in 9.35 g of dimethylformamide
was added dropwise to this suspension at 5 to 10C for
1.5 hours. Thereafter, the resulting mixture was stirred at
room temperature for 1 hour, and then a solution of 8.42 g
(0.0291 mole; E/Z=99.8/0.2) of (E)~ 4-chlorophenyl)-2-
(1,2,4-triazol-1-yl)-4,4-dimethyl-1-penten-3-one in 49.7 g
of chlorobenzene was added at room temperature. The
resulting mixture was stirred at the same temperature for
18 hours. The reaction solution was decomposed with
addition of 17.50 g of 10% hydrochloric acid and 5 g of
water, and the organic layer was separated, washed with
water and concentrated under reduced pressure to obtain 8.15
g (~)-(E)-1-(4-chlorophenyl)-2-(1,2,4-triazol-1-yl)-4,4-
dimethyl-1-penten-3-ol as a crystal. The conversion was
99.8%, and the composition of the product obtained was:
E-form alcohol, 90.8%; saturated alcohol, 2.3%; and Z-form
alcohol, 6.9~. The enantiomer ratio of the E-form alcohol
was: (+)-isomer, 81.0% and (-)-isomer, 19.0%. The optical
yield was 62.0~.
Example 43
In a nitrogen atmosphere, a solution of 2.64 g
(0.0698 mole) of sodium borohydride in 14.95 g of dimethyl-
formamide was added dropwise at -20C to a suspension of
13.07 g (0.0696 mole) of (~)-norephedrine hydrochloride in
52.26 g of 1,2-dichloroethane, and the temperature of the
- 36 -

~Z~1~)97
1 resulting mixture was raised from -20C to room temperature
over 2 hours.
Thereafter, 0.35 g of phosphoric acid and then a
solution of 16.12 g (0.0497 mole) of (E)-1-(2,4-dichloro-
phenyl)-2-(1,2,4-triazol-1-yl)-4,4-dimethyl-1-penten-3-one
(E/Z=97.6/2.4) in 49.37 g of 1,2-dichloroethane were added
at 20 to 25C, and stirring was carried out at the same
temperature for 20 hours. The reaction solution was
decomposed with addition of 24.17 g of 20% nitric acid and
4.6 g of water, and the organic layer was separated, washed
with water and concentrated under reduced pressure to obtain
15.60 g of (-)-(E)-1-(2,4-dichlorophenyl)-2-(1,2,4-
triazol-l-yl)-4,4-dimethyl-1-penten-3-ol as a crystal. The
conversion was 99.8%, and the composition of the product
obtained was: E-form alcohol, 95.6%; saturated alcohol,
0.4%; Z-form alcohol, 3.2%; and others, 0.8%. The
enantiomer ratio of the E-form alcohol was: (-)-isomer,
85.8% and (+)-isomer, 14.2%. The optical yield was 71.6%.
Example 44
In a nitrogen atmosphere, 0.338 g (1.8 mmoles) of
(-)-norephedrine hydrochloride was suspended in a mixture
comprising 15.4 ~1 (0.27 mmole) of acetic acid and 5 ml of
1,2-dichloroethane, and after cooling to -30C, a solution
of 0.0749 g (1.98 mmoles) of sodium borohydride in 1 ml of
dimethylformamide was added. The temperature of the
resulting suspension was raised from -30C to room tempera-
ture over 2 hours. Thereafter, to this suspension was

~.2~C~
1 added at room temperature a solution of 0.31 g (1.2 mmoles)
of (E)-1-cyclohexyl-4,4-dimethyl-2-(1,2,4-triazol-1-yl~-
1-penten-3-one (E/Z=99.9/0.1) and 10.3 ~1 (0.18 mmole) of
acetic acid in 1,2-dichloroethane, and stirring was carried
out for 24 hours. The subsequent treatment was carried
out in the same manner as in Example 6 to obtain (-)-(E)-
l-cyclohexyl-4,4-dimethyl-2-(1,2,4-triazol-1-yl)-1-penten-
3-ol. The conversion was 100%, and the composition of the
product obtained was: E-form alcohol, 97.4% and Z-form
alcohol, 2.6%. The enantiomer ratio of the E-form alcohol
was~ isomer, 77.7% and (+)-isomer, 22.3%.
E~ample 45
In a nitrogen atmosphere, a solution of 0.272 g
of (+)-norephedrine in 4 ml of 1,2-dichloroethane was added
dropwise at -78C to a mixture comprising 1.8 ml of a
0.500M diborane-tetrahydrofuran solution and 2 ml of
1,2-dichloroethane, and the temperature of the resulting
mixture was raised from -78C to room temperature over about
2 hours. Thereafter, to this solution was added dropwise at
room temperature a solution of 0.39 g of (E)-1-(2,4-
dichlorophenyl)-2-(1,2,4-triazol-1-yl~-4,4-dimethyl-1-
penten-3-one (E/Z=99.9/0.1) in 4 ml of 1,2-dichloroethane,
and stirring was carried out for 24 hours. Thereafter,
6 ml of 2M hydrochloric acid was added to the reaction
solution, followed by stirring for about 2 hours. The
organic layer was washed with water, dried over anhydrous
sodium sulfate and concentrated under reduced pressure.
- 38

g7
1 The residue was purified on a column packed with 2 g of
silica sel using a chloroform solvent and then concentrated
under reduced pressure to obtain 0.39 g of (-)-(E)-l-
(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-yl)-4,4-dimethyl-
S l-penten-3-ol as a crude crystal. The conversion was 98.6%,
and the composition of the product obtained was: E-form
alcohcl, 98.6~ and Z-form alcohol, 1.4%.
Optical rotation [~]D: -20.7 (c=1.0, CHC13)
Optical yield of E-form alcohol: 70
Examples 46 to 50
Reaction was carried out according to Example 45
using the following reac~ion solvents in place of 1,2-
dichloroethane, to obtain (-)-(E)-1-(2,4-dichlorophenyl)-
2-(1,2,4-triaæol-1-yl)-4,4-dimethyl-1-penten-3-ol. The
results are shown in Table 9.
- 39 -

~2~V~7
o ~ o
h ~ _ ~r ~r t:~ co L~
q~ u~ ~ L~ ~D n
O '~ ~ ~
~ CO o ~ o o
~) ~ ~~ ,_1 ~1 ~r u~ ut ~1
C~ .~ . . . .
~ ~ ~ ~O ~r ~ o
~0 oO~OU _l ~ ~ ~ l
~ ~'.C
.~ O O
U I 1~ t~l ~ W f'~
~ ~ O ~ o o o
0~0\ ~ OD a~ ~ c7~
d~ --O O ~ O
a~ ~:: 0 ~ cn 10 ~ ~i
,4 _
E~ r
~) ~ a~ ~r _l
e s _,
'~
_
s~ ~
r~l~ ~ ~a~ o
~ ~ ~ ~ ~ a) ,ra ~ ~
_~ ~ a~ ~ s~ o
a~ o :~ x ~ .c o R S-
~; ~q .C O ~ ~ ~1 5
.,, o a~
. _ r~ a E~ ~ O U
~ z W ~ ao a~ o
1i3 _
-- 40 --

97
1 Examples 51 and 52
Reaction was carried out in the same manner as
in Example 45 except that toluene was used as reaction
solvent in place of 1,2-dichloroethane, the reaction time was
changed to 23 hours, and that the molar ratio of diborane
to (+)-norephedrine was varied, to obtain (-)-(E)-1-(2,4
dichlorophenyl)-2-(1,2,4-triazol-1-yl)-4,4-dimethyl-1-
penten-3-ol. The results are shown in Ta~le 10.
- 41 -

~LZ;~ 7
_ _
~ ~ e ,, ~r
'~ 'I ~ ' 117 n
~3 I h
O ~ O ~ ~ ~r
h ~ O I ~
i` ~D
~0 ~ ~ ~0 (~
.~ _ .
^ Ul o~
~; ~ O ~P ~i O
~ _
~,C - U~
O O dP
,01 ~ ~ cn
R O
E~ ~ ~P ~ ~o
~ _ ~ ~
\ 'S~ O O
\ ~1 ~i ,_1
~ \ + O ~ r o
a
_ _
~ ~3
.
-- 42 --

~L221(397
1 Examples 53 to 57
Reaction was carried out in the same manner as in
Example 45 except that the optically active amino alcohols
described below were used in place of (+)-norephedrine,
and that tetrahydrofuran and diethyl ether were used as a
reaction solvent. The results are shown in Table 11.
- 43 -

:12~1~97'
~ N N N r O
r~ ~ O O dP ~ ~ O ~ ~
o a) v~ t~l ~ ~. ~ ~,
~rl I r-l
0~
~ + ~ ~ ~ ~ O
~--~ . . . .
~ O I 0~1 er ~ u~ U~
~1 ~ -- -- -- --
O I ,C ~r a~ C5~ a~ o
O ~ rl q O . . . .
~1t~ ~ U Is~ ~ ~r ~ CD
~ ~0~ _ _
.,1~
O
s~ ~ _ ~ ~ r ~r c~
~0 C~ O O O O ,_
t~1; _
~ O
h ~ ~ ~ a~ tr7 ~D ~
00 ~ . . . .
_ a~ ~ cr~ c~ co
a~ ~ ~
_ _
s~ ~o ~ ~r o~
oP ~o o ~r O ~
o~ ,1 - 0~ O ~` ~ CO
C~
R I ,_
E~ C~ ~ I~ er O
~ O ~ S ,1 ~ ~ ~
~ ~ ~1 ~1
. _
, O O O
~ S~ S~ 5
O ~ ~ ~
~ ~ ~ S~ _~ S
O ~ ~ ~ S S~ ~ ~ S ~ ~ ~
r~ ~1 ~ rd ~ n~ ~ ~ ~ ~ 5~ td
~ O ~ ~ au ~ ~ h ~ S ~ 5~
~n a~ ~ 1 ~~J 3 .rl ~ a~
E~ ~ a) E~ ~ C~ a~ E~
~ ~ ~ ~ l l l
a) 'ol '~ ~ .~ ~ ~ ~ ~ol
~ ~ o s o o ~ o ~ ~ a~
.,, ~1 ~ o a) ~ ~ ~ ~ ~ I ~ ~ ~
~ s~ c~ ~ s~ s ~ ^ Q, ~ s
O ~ ~1 I S ~ u~ I S ~ tn +-rl I
o ~ ~ ~ ~ ~ ,
~ -
P O ~ ~r u~ ~D I~
~ Z u~ u~ ~ In U~
~ . _
-- 44 --

lz~as~
1 Examples 58 and 59
Reaction was carried out in the same manner as in
Example 45 except that (+)-norephedrine was replaced by
~ norephedrine and (E)-1-(2,4-dichlorophenyl)-2-(1,2,4-
triazol-1-yl)-4,4-dimethyl-1-penten-3-one, and that the
following ketone compounds were used. The results are
shown in Table 12.
- 45 -

lL~ZlV9~7
a t ~
S~ ~D
~
~_ r o
a~ ~lo
~ 5~ =~
~U ; ~3~D
_ _
~ _ U~ l
-- 46 --

Z1~9~
. _ ~
CO CO
a)~ a~
,o- o-OI oo
O I S _l a~
3 o .
~ ~ ~, U~
,_ C ~ 4~ ,,
~ ~ o
Yo _
~, ~,~
_l ~ ~D
~ ,,
,~o _~
~ ~S- _, o
~ O Od~ .
o ~_ ~ _,
~ ~o~ l
~o~ ~
-- 47 --

~=
Examples 60 to 69
Asymmetric reduction was carried out in the same
manner as in Example 6 except that (+)-norephedrine hydro-
chloride was replaced by an amino alcohol of (+)-2-amino-
1-(2,5-dimethoxyphenyl)-1-propanol hydrochloride, (+)-2-
amino-l-(2,5-diethoxyphenyl)-1-propanol hydrochloride, (-)-
2-amino-1-(2,4-dimethoxyphenyl)-1-propanol hydrochloride,
(+)-2-amino-1-(2-methoxyphenyl)-1-propanol hydrochloride
or (-)-2-amino-1-(2-ethoxyphenyl)-1-propanol hydrochloride,
to asymmetrica~ly reduce a ketone compound of (E)-l-
(4~ chlorophenyl)-2-(1,2,4-triazol-1-yl)-4,4-dimethyl-1-
penten-3-one (E/Z= 98.9/1.1), (E)-l-cyclohexyl-2-(1,2,4-
triazol-l-yl)-4,4-dimethyl-1-penten-3-one (E/Z=99.9/0.1)
or (E)-1-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-yl)-
4,4-dimethyl-1-penten-3-one (E/Z=97.6/2.4). The results
are shown in Table 13.
- 48 -
~i

~ ~ h ~, ,Q o ~l O
0 10- Co Cl` ~ I I O
~+ O ~ rO
~ , l l _
~ ~ O` C~ O
+~ ~, r ~ ~ ~ I ~i ~i ~
~ ~J ~ ,
~C~0~1 V' ~1 1 l V
~ ~ h 0
I _
~ eS ~ ~ O`
_ ~ 0 ! - _
~ ~O` Nl O ! `
~ o~ ~ ~ ! ~ ~ l ~ L
~} ~an o o ~ o ~ o
*~ *~--æ
o ~ æ ~ ~ ~ ~
a ~ = = c~ o~ ~ l _ o
~ ~ ~ l +
~æ ~
_ 49 _

~221~)97
~ I ~ ~o
~ r .
_ , _
~ ~ I ~.' ~o ~
V I ~ ~ V V ~
o c~ ~ e
o
o I oo CY I o o ~
~o ~ ~ ~
O I O O ~O _ C~I
Xl ~ ~ _ 3~ o~
æ >~ I_~*~1 ~ ~ I :r ~
~\0 0 ~ ~-0 = Co~-~
+ ~ + ~ 1
ô ~ w~ ~ ~ ~
o--o z o--~ z ~ o_~ æ J
~z~J ~ æ \c~/\æ
,~
~o ~ ~ ~ ~o
-- 50 --

12~097
Example 70
Under a nitrogen atmosphere, 0.4459 g (1.8 mmoles)
of (-)-erythro-2-amino-1-(2,4-dimethoxyphenyl)-1-propanol
hydrochloride (optical purity, 98.6%) was suspended in 5 ml
of 1,2-dichloroethane, the suspension was cooled to -25~C, and
af-ter addlng a solution of 0.0681 g (1.8 mmoles) of sodium
borohydride in 1 ml of dimethylformamide, the temperature
was raised from -25C -to room temperature over 2.5 hours.
Thereafter, to -this suspension was added at 20C a solution
of 0.35 g (1.2 mmoles) of (E)-1-(4-chlorophenyl)-2-(1,2,4-
triazol-l-yl)-4,4-dimethyl-1-penten-3-one (E/Z=98.9/1.1) in
4 ml of 1,2-dichloroethane, and the mixture was stirred for
26 hours. Thereafter, decomposition was carried out at 45C
with stirring with addition of 8 ml of 10% hydrochloric acid.
The organic layer was washed with water, dried over anhydrous
sodium sulfate and concentrated under reduced pressure to
obtain 0.35 g of a crude crystal of (+)-(E)-1-(4-chlorophenyl)-
2-(1,2,4-triazol-1-yl)-4,4-dimethyl-1-penten-3-ol. Gas
chromatographic analysis showed that the conversion was 97.8%
and that the product composed 95.7% of the E-form alcohol
and 4.3% of the Z-form alcohol. High-performance liquid
, chromatography on optically active column showed that the
i enantiomer ratio of the E-form alcohol was: (~)-form, 85.0%;
and (-)-form, 15.0~.
Reference Examples 1 to 7
.
Reference Example 1
To a mixture of 8.43 g (0.04 mole) of (-~)-erythro-
-2-amino-1-(2,4-dimethoxyphenyl)-1-propanol (ery-thro/threo=
98.9/1.1) and 60 ml of water was added 5.21 g (0.04 mole)
of D-(-)-pantolactone, and after stirring at 80 to 90 C for
1 hour, the reaction solution was concentrated under reduced
pressure. The residue obtained was recrystallized from 50
- 51 -

ml of methanol ethanol (1:4) mixture to obtain 5.44 g of
the diasteroemer salt of D-(-)-pantolc acid. [~]D: -16.0
(c=l.0, water). This product was recrystallized once more
from 50 ml of ethanol to ob-tain 3.64 y of D~ pantoic acid
acid salt of (-)-erythro-2-amino-1-(2,4-dimethoxyphenyl)-1-
propanol. [~]D: -19.4 (c=l.0, water). The dias-tereomer
salt obtained was decomposed with a solution of 1 g of pot-
assium hydroxide in 10 ml of water and extracted with methy-
lene chloride to obtain 2.07 g of (-)-etythro-2-amino-1-(2,
4-dimethoxyphenyl)-1-propanol (erythro/threo= 99.6/0.4). m.p. :
92-93C. The optical purity of this product was 98.6% by
high-performance liquid chromatographic analysis. By dissol-
ving -this arninoalcohol in a mixed solvent of diethyl ether
and methylene chloride and passing a hydrogen chloride gas
therethrough, 2.36 g of (-)-erythro-2-amino-1-(2,4-dime-thoxy-
phenyl)-l-propanol hydrochloride was obtained. m.p. : 183-
183.5C (decomp.). [~]D: ~34 0 (c=l.0, water). The optical
purity of this product was 98.6% by high-performance liquid
chromatographic analysis.
Reference Example 2
A mixture of 14.05 g of (+)-erythro-2-amino-1-(2-
methoxyphenyl)-l-propanol (erythro/threo=98.0/2.0), 10.09 g
of D-(-)-pantolactone and 100 ml of water was heated for 1
hour with stirring and concentrated under reduced pressure.
The residue obtained was recrystallized from 110 ml of iso-
propanol to obtain 5.09 g of the D-(-)-pantoic acid salt of
(+)-erythro-2-amino-1-(2-methoxyphenyl)-1-propanol. [~]D
` 30 +22.9 (c=0.9, water). This dias-tereomer salt was decomposecL
with a solution of 1.61 g of potassium hydroxide in 20 ml of
water and extracted with chloroform to obtain 2.58 g of (+)-
erythro-2-amino-1-(2-methoxyphenyl)-1-propanol. By dissolv-
- ing this aminoalcohol in diethyl ether-chloroform mixture ancL
passing a hydrogen chloride gas therethrough, the hydrochloric
; acid salt of the aminoalcohol was formed. This salt was
;
- 52 -

3L~21~)97
collected by filtration and dried to obtain 2.82 g of (~
erythro-2-amino-1-(2-methoxyphenyl)-1-propanol hydrochloride.
[a~D: +26.5 (c=1.0, water). This product was conver-ted to
its sugar derivative (diastereomer) and analyzed by high-
performance liquid chromatography to find that i-ts optical
purity was 62.6%. The filtra-te after recrystalliza-tion was
concentrated under reduced pressure to obtain 20.28 g of the
D-(-)-pantoic acid salt of (-)- erythro-2-amino-1-(2-methoxy-
phenyl)-l-propanol. [a]D: +1.29 (C=1.0, water). This product
was recrystallized from isopropanol, and after filtration,
the filtrate obtained was concentrated under reduced pressure,
decomposed with a solution of 3.76 g of potassium hydroxide
in 47 ml of water and extracted with chloroform to obtain
6.79 g of (-)-erythro-2-amino-1-(2-methoxyphenyl)-1-propanol.
This aminoalcohol was converted -to its sugar derivative (dia-
stereomer) and analyzed by high-performance liquid chroma-to-
graphy to find that its optical purity was 44.6%. ~3y dissolv-
ing this aminoalcohol in diethyl ether-chloroform mixture and
passing a hydrogen chloride gas therethrough, (-)-erythro-2-
amino-1-(2-methoxyphenyl)-1-propanol hydrochloride was ob-
tained. After recrystallizing this hydrochloride three times
from ethanol, 1.75 g of (-)-erythro-2-amino-1-(2-methoxyphenyl)-
l-propanol hydrochloride was obtained from the filtrate. Ca]D:
-37.7 (c=1.0, water). The optical purity of this product was
98.0% by high-performance liquid chromatographic analysis.
Reference Example 3
On adding a hot solution of 20.5 g (0.0918 mole)
of (+)-erythro-2-amino-1-(2,5-diethoxyphenyl)-1-propanol
(erythro/threo=98.4/1.6) in 40 ml of methanol to a hot solu-
tion of 13.78 g (0.0918 mole) of L-(+)-tartaric acid in 50
ml of methanol, a crystal was deposited. This crystal was
re-dissolved in the solution by additionally adding 140 ml
of methanol, and after allowing to cool, the deposited crystal
was collected by filtra-tion. The yield of the crystal was
- 53 -

~2~0~
12.43 g- [~]D: +28.0 (c=1.0, water~. This crystal was fur-
ther recrys-tallized from 150 ml of methanol to obtain 7.44 g
of the I,-(+)-tartaric acid salt of (+)-erythro-2-amino-1-(2,5-
diethoxyphenyl)-l-propanol. [~]D +31.8 (c=1.0, water).
This salt was decomposed with a 10% aqueous sodium hydroxide
solution and extracted with methylene chloride to obtain 4.75
g of (+)-ery-thro-2-amino-1-(2,5-diethoxyphenyl)-1-propanol
(erythro/threo=100/0). By dissolving this product in diethyl
ether and passing a hydrogen chloride gas therethrough, 5.40
g of (+)-erythro-2-amino-1-(2,5-diethoxyphenyl)-1-propanol
hydrochloride was obtained. m.p.: 136.5-138.5 C. [~]D: +29.i
(c=l.0, water). The optical purity of this product was 99.0%
or more by high-performance liquid chromatographic analysis.
Reference Example 4
A hot solution of 11.19 g of (+)-erythro-2-amino-1-
(2-ethoxyphenyl)-1-propanol (content of the erythro-form,
99~ or more) in 15 ml of methanol was added to a hot solu-
tion of 8.60 g of L-(+)-tartaric acid in 20 ml of methanol,
and the resulting solution was allowed to cool. The deposi-
ted crystal was collected by filtration to obtain 10.44 g
of the L-(-~)-tartaric acid salt of (-)-erythro-2-amino-1-
(2-ethoxyphenyl)-1-propanol. [ ~]D: +6-3 (c=1.0, water). This
sal-t was recrystallized from methanol to obtain 4.50 g of
a crystal. [~JD -16.4 (c=l.0, CHC13). This aminoalcohol
was converted to its sugar derivative (diastereomer) and
analyzed by high-performance liquid chromatography to find
that its optical purity was 63.2%. By dissolving this amino-
alcohol in diethyl ether-chloroform mixture and passing a
hydrogen chloride gas therethrough, 3.18 g of (-)-erythro-
2-amino-1-(2-ethoxyphenyl)-1-propanol hydrochloride was
obtained. Recrystallization of this product from isopropanol
was repeated four times to obtain 1.02 g of a crystal. [~]D
-43.6 (c=l.0, water). The optical purity of the crystal
was 97.8%.
- 54 -

~Z~ 9~
eference Example 5
On adding a solution of 4.56 g (0.0263 mole) of
N-acetyl-L-leucine and 1.11 g (0.0263 mole) of 95% sodium
hydroxide in 50ml of wa-ter to a solution of 12.17 g (0.0525
mole) of (+)-erythro-2-amino-(2-methoxy-5-me-thylphenyl)-1-
propanol hydrochloride (ery-thro-form, 99% or more) in 115 mL
of water, a crystal was deposited. This crystal was re-
dissolved in the solution by additionally adding 500 ml of
water, and after allowing to cool, the deposited crystal was
collected by filtra-tion. The yield of the N-acetyl-L-
leucine sal-t of (-)-erythro-2-amino-1-(2-methoxy-5-methyl-
phenyl)-l-propanol was 3.63 g. [a]D: -29.2 (c=1.0, water).
This salt was decomposed with a 10% aqueous sodium hydroxide
; 15 solution and extracted with chloroform to obtain 1.94 g
of (-)-erythro-2-amino-1-(2-methoxy-5-methylphenyl)-1-pro-
panol- [~]D: -22.1 (c=l.l, CHC13)i By dissolving this pro-
duct in diethyl ether and passing a hydrogen chloride gas
therethrough, 2.13 g of (-)-erythro-2-amino-1-(2-methoxy-5-
methylphenyl)-l-propanol hydrochloride was obtained. This
salt was recrystallized from isopropanol to ob-tain 1.65 g
of the crystal. [~]D: -22.2 (c=1.0, water). The optical
purity of this product as sugar derivative (diastereomer)
was 97.8% by high-performance liquid chromatographic analysis.
;
Reference Example 6
31 Grams (0.114 mole) of 2-amino--1-(2,5-diethoxy-
phenyl)-l-propanone hydrochloride was dissolved in 450 ml
of water, and 2.15 g (0.0568 mole) of sodium borohydride was
added at 3 to 7C. After maintaining the temperature for
2 hours with stirring, the reaction solution was acidified
with conc. hydrochloric acid and washed with chloroform.
The aqueous layer was made alkaline with a 25% aqueous sodium
hydroxide solution and extracted with chloroform to obtain
24.1 g of (+)-erythro-2-amino-1-(2,5-diethoxyphenyl)-1-
- 55 -

7.
propano] (erythro/threo=93.6/6.4). This product was recrys--
tallized from toluene -to obtain 21.0 g of a crystal (erythro/
threo=98.4/1.6).
m.p., 108-109C
NMR spectrum (CDC13):
(ppm): 0.99 (d 3H), 1.37 (t 6H), 1.4-2.2 (broad
2H), 3.24 (m H), 3.98 (q 4H), 4.72 (d H), 6.74 (2H),
6.96 (H)
Reference Example 7
20 Grams (0.0938 mole) of 2-amino-1-(2-ethoxy-
phenyl)-l-propanone hydrochloride was dissolved in 300 ml of
water, and 1.77 g (0.0468 mole) of sodium borohydride was
added at 5 to 8C. After maintaining -the temperature for
1 hour with stirring, the reaction solution was allowed -to
stand overnight at room temperature. Thereafter, the reac-
tion solution was acidified with conc. hydrochloric acid and
then made alkaline with a 25% aqueous sodium hydroxide solu-
tion. The deposited crystal was collected by filtration,
washed with water and dried to obtain 13.40 g of erythro-2-
amino-1-(2-ethoxyphenyl)-1-propanol as a crystal (erythro/
threo=98.4/1.6). This crystal was recrystallized from to-
; luene to obtain 12.39 g of a crystal (content of the erythro--' 25 form, 99% or more).
m.p., 89-91C
NMR spectrum (CDC13):
~(ppm): 0.99 (d 3H), 1.40 (t 3H), 1.6-2.4 (broad
2H), 3.24 (m E-l), 3.99 (q 2H), 4.76 (d H), 6.7-7.04
(m 2H), 7.05-7.45 (m 2H)
'
- 56 -
, .
.,