Note: Descriptions are shown in the official language in which they were submitted.
R'O 96109283 2 ~ 7 6 9 6 0 PCTIKR95I00124
NOVEL CARBAMATE COMPOUNDS AND PROCESSES FOR PREPARING
THE SAME
BACRGROUND OF THE INVENTION
Field of the invention
The present invention relates, in general, to novel
enantiomeric carbamate compounds pharmaceutically useful
for central nervous disorders and, more particularly, to
(S)-2-aryl-1,3-propanediol monocarbamate derived from (R)-
3-acetoxy-2-arylpropanol carbamate and to (S)-3-acetoxy-2-
aryipropanol carbamate, its intermediate. Also, the
present invention is concerned with processes for
preparing the novel carbamate compounds.
Description of the Prior Art
Carbamates have been effectively used for controlling
central nervous system (hereinafter referred to as "CNS")
disorders, especially, as an antiepiletic and a centrally
acting muscle relaxant. For example, 2-methyl-2-propyl
1,3-propanediol dicarbamate was reported in J. Am. Chem.
Soc., 73, 5779 (1951), and the pharmaceutical activity
thereof was ascertained in J. Pharmacol. Exp. Ther., 104,
229 (1952).
U.S. Pat. No. 3,256,728 discloses that the compounds,
represented by the following general formula A, are
pharmaceutically useful therapeutics for CNS disorders.
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2
R
Rz [A] '
~ R3
Z
wherein, R1 is a carbamate or methylene carbamate; RZ is
an alkyl group containing one or two carbon atoms, a
hydroxy alkyl group containing one or two carbon atoms,
hydroxy or hydrogen; R3 is hydrogen or an alkyl group
containing one or two carbon atoms; and Z represents a
halogen such as fluorine, chlorine, bromine or iodine, a
methylmethoxy group, a phenyl group, a vitro group or an
amine group.
Besides, other carbamate compounds which are very
useful therapeutic medicines against CNS disorders, in
particular, as antiepiletic and centrally acting muscle
relaxant, ate disclosed, including 2-phenyl-1,3-
propanediol dicarbamate in U.S. Pat. No. 2,884,444 and
isopropyl meprobamate in U.S. Pat. No. 2,937,119. At
present, various researches for such carbamate compounds
are being actively continued in the art.
SUMMARY OF THE INVENTION
Based on intensive and thorough study and research
by the present inventors, it was found that the carbamate
compounds represented by the following structural formulas
I and II are useful for the treatment and prevention of
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3
CNS diseases including nervous myalgia, epilepsy and
' cerebral apoplexy:
R ~ CH20H
[I]
CHZOCONHZ
R CH2OCOCH3
[II]
CHZOCONHZ
wherein, R is
O O Y O Y O XY O XY
' ' Y ' ' YX '
Y Y XY XY
r C~ or YX--~
N , N , , , N
wherein X is an oxygen atom or a sulfur atom; and Y
repre°- is a halogen element, trifluoromethyl, or a lower
alkyl ~~oup containing one to three carbon atoms.
In addition, taking advantage of the far superior
activity of single enantiomeric isomer to racemic mixture
in biological systems, the present inventors developed the
enantiomers of Formulas I and II, which had never been
WO 96109283 217 6 9 6 0 PCT~~00124
4
found, and applied them as pharmaceutically active
ingredients against CNS diseases.
The carbamate compounds of Formulas I and II are
chiral molecules with a chiral center of carbon at 2
propyl and may have either an (S) or (R)-configuration.
Accordingly, it is an-object of the present invention
to provide novel (S)-enantiomeric compounds represented
by Formulas I and II-, which have pharmaceutically useful
activity against central nervous system diseases.
It is another object of the present invention to
provide a method for preparing the compounds of Formulas
I and II at high yield and high purity within a short
time.
DETAILED DESCRIPTION OF THE INVENTION
The compound of Formula II can be prepared by
treating (R)-3-acetoxy-2-aryl-propanol, represented by the
following formula III:
R CHZOCOCH3
[III]
CHZOH
wherein, R is as defined above, with phosgene in a mixture
of aromatic hydrocarbon and halogenohydrocarbon in the
presence of amine base, and followed by anhydrous ammonia.
Available aromatic hydrocarbons include benzene,
WO 96109283 2 ~ 7 6 9 6 0 PCT/KR95/0012~1
toluene and xylene and a halogenohydrocarbon is selected
' from the group consisting of chloroform, dicholomethane,
1,2-dichloroethane and trichloroethane. The preferred
solvent is a mixture of toluene and dichloromethane.
5 As the amine base, antipyrine, diisopropylethylamine,
diethylamine, triethylamine or pyridine is available, with
a preference to such a sterically hindered base as
triethylamine, diisopropylethylamine or antipyrine.
Temperature is maintained at -30 to 0 'C upon
reaction with phosgene while the reaction with anhydrous
ammonia is carried out at a temperature of -70 to 0 'C.
For use, anhydrous ammonia is condensed to a liquid.
It is added at an excess of 10 to 100 equivalents and
preferably at an excess of 25 to 50 equivalents.
In accordance with the present invention, the
compound of Formula I can be converted from (S)-3-acetoxy-
2-aryl-propanol carbamate, represented by Formula II,
through the catalytic reaction of hydrolase in a buffer
solution. High yield and optical purity can be
accomplished within a short time by the enzymatic
hydrolysis of (S)-3-acetoxy-2-aryl-propanol carbamate into
(S)-2-aryl-1,3-propanediol monocarbamate.
Generally, enzymes show a far higher catalytic
activity than chemical catalysts while giving less by-
products.--In addition, since the enzymatic conversion
of
(S)-3-acetoxy-2-arylpropanol carbamate into (S)-2-aryl-
1,3-propanediol monocarbamate is carried out at a low
WO 96109283 t ' y ~ 2 l 7 6 9 6 0 PCT/KR95100124
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temperature in a neutral aqueous solution, for example,
phosphate buffer solution, the side-reactions attributable '
to the enzyme can be eliminated. Following the
hydrolysis, the enzyme used can be almost completely
removed only by filtration without lowering the product
yield. Accordingly, the present invention is very
advantageous in time and cost.
In more detail, the (S)-3-acetoxy-2-arylpropanol
carbamate of Formula II is dissolved in a phosphate buffer
solution and then, vigorously stirred at a temperature of
0 to 35 'C and with ordinary pressure in the presence of
hydrolase. Preference is given to a temperature of 10 to
25 'C. Care must be taken to control the reaction
temperature. A reaction temperature of higher than 35 'C
makes the hydrolysis proceed faster but causes the enzyme
to be lowered in selectivity, deleteriously affecting the
optical purity of the product.
The phosphate buffer solution has a pH ranging from
6 to 9 with a preference of 7. For example, if the
phosphate buffer solution has a pH of higher or lower than
7, the optical purity of the product becomes poor. In
order for the selectivity of the enzyme not to be lowered,
the phosphate buffer solution is preferably diluted into
0.01 to 0.1 mole solution.
With regard to the hydrolase used for the conversion,
various sources are available. Representative examples
include lipase extracted from pig's pancreas (PPL),
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Candida lipase (CCL), Aspagillus lipase (ANL), Pseudomona5
' lipase (PSL) and an esterase from pig's liver (PLE), with
a preference for PLE.
Usually at 4 to 5 hours after adding the enzyme, the
conversion reaction of (S)-3-acetoxy-2-aryl-propanol
carbamate into (S)-2-aryl-1,3-propanediol monocarbamate
is terminated. Thin layer chromatography or high
performance liquid chromatography may be used to determine
the termination point of the conversion reaction.
From the resultant reaction mixture, the enzyme may
be filtered off simply and then, the solvent is removed
by using a rotary evaporator. Purification by column
chromatography gives (S)-2-aryl-1,3-propanediol
monocarbamate of Formula I, a novel compound.
Likewise, (R)-3-acetoxy-2-aryl-propanol of Formula
III can be prepared by use of an enzyme. For this, PPL,
CCL or PSL is immobilized to cellite. Preference is given
to PPL and PSL_ 2-aryl-1,3-propanediol is dissolved in
anhydrous alkyl acetate, such as methyl acetate, ethyl
acetate, propyl acetate and vinyl acetate, or anhydrous
alkenyl acetate and incubated at a temperature of -10 to
35 'C. Following this, the reactant is added with the
immobilized catalyst system in the absence of solvent
while vigorously stirring. At this moment, the reaction
is carried out preferably at a temperature of 0 to 35 'C
under ordinary pressure. Particularly, care must be taken
to control the temperature below 35 'C because higher
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temperature makes the reaction proceed too fast, resulting
in degradation of optical purity.
High performance liquid chromatography can also be
used about 3 hours-after the reaction, to determine the
termination of the reaction. Five hours after the
reaction is usual-ly enough to obtain the compound of
Formula III with a yield of 85 % or larger and an optical
purity of 99 % or more.
To identify (S)-2-aryl-1,3-propanediol monocarbamate
as a pharmaceutically useful material, anticonvulsant
activity assay of the novel compound of the present
invention was executed through standard Maximal Electro
Shock (MES) test. To the end, 0.5 g (S)-2-phenyl-1,3
propanediol monocarbamate was suspended in 100 ml buffer
solution at pH 7.4. The prepared suspension was
administered into ten male CD-2 mice weighing about 20 to
g at a dose of 300 mg/kg. Oral administration through
a syringe is preferred. At one hour after administration,
the middle of the forehead of the mice was electrically
20 shocked at 50 mA for 0.2 second by use of corneal
electrode. Of the ten mice administered with the compound
of the present invention, nine were not convulsed and
acted as usual_ Only one was convulsed. to death.
A better understanding of the present invention may
25 be obtained in light of following examples which are set
forth to illustrate, and are not to be construed to limit,
the present invention.
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EXAMPLE I
(S)-3-Acetoxy-Z-(2-pyridyl) propanol carbamate
500 ml flask equipped with a thermometer was well
dried and purged by flowing nitrogen gas into the inside
thereof for 30 min. After the moisture and air present
within the flask was replaced by nitrogen gas, 24.5 mI of
0.6 M phosgene solution was placed in the purged flask,
followed by the addition of 150 mI of toluene. The flask
was maintained at -30 'C in a bath containing dry ice and
acetone.
Separately, 2.0 g of (R}-3-acetoxy-2-(2-
pyridyl)propanol and 4.7 g of antipyrine were placed in
100 ml flask well dried. To this, 70 ml chloroform was
added.
To the phosgene/toluene solution maintained at -30
'C, the (R)-3-acetoxy-2-(Z-pyridyl) propanol solution was
dropwise added with a double-ended needle. Following the
completion of addition, thin layer chromatography was
executed to know whether the starting materials were
completely exhausted. Then, the reaction system was
cooled to -70 'C and slowly added with 50 g of liquid
ammonia. Reaction proceeded at -70 'C while stirring.
Excess ammonia present in the reaction mixture was blown
off by nitrogen gas at about 2 hours after the completion
of reaction. While precipitate was filtered off and the
W O 96109283 y ,, . j ~ ~ 7 6 ~ 6 p PCT/HIt95/0012~1
solvents, toluene and chloroform, were removed by use of
a rotary evaporator.
The resultant concentrated solution was subjected to
column chromatography (mobile phase: ethyl acetate),
5 giving forth (S)-3-acetoxy-2-(2-pyridyl) propanol
carbamate: Yield 84.0 $, purity 99.8 $.
Physical Properties of (S)-3-acetoxy-2-(2-pyridyl)
propanol carbamate: [a] _ + 45.3 ' (0.42 in acetone)
1H-NMR (CDC13, 200 MHz), ppm (b): 1.99 (s, 3H), 3.52
10 (q, IH), 4.43(m, 4H), 5.25 (br, 2H), 7.21(m, 2H), 7.68(m,
1H), 8.56(d, 1H)
EXAMPLE II
(S)-3-Acetoxy-2-(2-(3-chloro)pyridyl) propanol carbamate
The title compound was prepared in a similar manner
to that of Example I, except that (R)-3-acetoxy-2-(2-(3-
chloro)pyridyl) propanol, instead of (R)-3-acetoxy-2-(2-
pyridyl) propanol, was used as a starting material: Yield
68.3$. Purity 98.5 $.
[aJ = + 53.1 ' (0.50 in acetone)
EXAMPLE III
(S)-3-Acetoxy-2-(Z-(3-trifluoromethyl)pyridyl) propanol
carbamate
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The title compound was prepared in a similar manner
' to that of Example I, except that (R)-3-acetoxy-2-(2-(3-
trifluoromethyl)pyridyl) propanol, instead of (R)-3
acetoxy-2-(2-pyridyl) propanol, was used as a starting
material: Yield 63.2%. Purity 99.3 %.
[a] _ + 24.7 ° (0.50 in acetone)
EXAMPLE IV
(S)-3-Acetoxy-2-(2-(3-methyl)pyridyl) propanol carbamate
The title compound was prepared in a similar manner
to that of Example I, except that (R)-3-acetoxy-2-(2-(3-
methyl)pyridyl) propanol, instead of (R)-3-acetoxy-2-(2-
pyridyl) propanol, was used as a starting material: Yield
76.8 %. Purity 99.3 %.
[o] _ + 15.3 ° (0.50 in acetone)
EXAMPLE V
(S)-3-Acetoxy-2-(2-(3-thiomethyl)pyridyl) propanol
carbamate
Except that (R)-3-acetoxy-2-(2-(3-thiomethyl)pyridyl)
propanol, instead of (R)-3-acetoxy-2-(2-pyridyl) propanol,
was used as a starting material, Example I was repeated
to give the title compound: Yield 67.3%. Purity 99.1 %.
WO 96!09283 ~ ~ , :' . ... 'c y. 217 6 9 6 0 PCT~5100124
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[a] _ + 37.8 ' (0.50 in acetone)
r
EXAMPLE VI
(S)-3-Acetoxy-2-(2-(4,6-dichloro)pyridyl) propanol
carbamate
Except that (R)-3-acetoxy-Z-(2-(4,6-dichloro)pyridyl)
propanol, instead of (R)-3-acetoxy-2-(2-pyridyl) propanol,
was used as a starting material, Example I was repeated
to give the title compound: Yield 70.1 %. Purity 99.2 %.
[a] _ + 48.3 ' (0.50 in acetone)
EXAMPLE VII
(S)-3-Acetoxy-Z-(2-(4,6-dimethoxy)pyridyl) propanol
carbamate
Except that (R)-3-acetoxy-2-(2-(4,6-
dimethoxy)pyridyl) propanol, instead of (R)-3-acetoxy-2-
(2-pyridyl) propanol, was used as a starting material,
Example I was repeated to give the title compound: Yield
72.9 %. Purity 98.9 %.
[n] _ + 24.1 ' (0.50 in acetone)
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EXAMPLE VIII
(S)-3-Acetoxy-2-phenylpropanol carbamate
In a Z50 mL flask equipped with a magnetic stirrer,
4.7 g of antipyrine (0.025 mole) and 1.94 g of (R)-3-
acetoxy-2-phenylpropanol (0.01 mole) were placed. 80 mL
of toluene and ZO mL of chloroform were poured into the
flask. The resulting reaction solution was maintained at
0 'C while stirring.
To the solution, 14 mL of 0.6 M phosgene was added
at 0 'C while stirring. White precipitate was evidence
that the reaction Was making progress. After five hours,
the reaction was terminated, and the reaction mixture was
subjected to filtration.
The filtrate was maintained at 0 'C and ammonia gas
was flowed into the flask for 30 minutes. After being
stirred for 30 minutes, the mixture was filtered to remove
precipitate. The solvents used were distilled off in
vacuo.
Isolation by column chromatography (using ethyl
acetate and n-hexane (1:1) as the mobile phase) gave (S)-
3-acetoxy-2-phenylpropanol carbamate: Yield 87.2 %. Purity
99.2 %.
Physical properties of (S)-3-acetoxy-2-phenylpropanol
carbamate: [a) _ + 2.5 ' (0.03 in CHC13)
ZS 1H-NMR (CDC13, 200 MHz), ppm (5): 1.99(s, 3H), 3.21-
WO 96109283 ~, , ~~ ~ -~ := 2 ~ 7 6 9 6 0 P~~SID0124
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3.37(m, 1H), 4.21-4.38(m, 4H), 5.14(b, ZH), 7.21-7.30(m,
5H)
EXAMPLE IX
(S)-3-Acetoxy-2-(o-chlorophenyl)propanol carbamate
The title compound was synthesized in a similar
manner to that of Example VIII, except that (R)-3-acetoxy-
2-(o-chlorophenyl) propanol, instead of (R)-3-acetoxy-2-
phenyl propanol, Was used as a starting material. Yield
63.1 %.,Purity 99.3 %.
[a] _ + 13.7 ' (0.50 in methanol)
EXAMPLE X
(S)-3-Acetoxy-2-(o-trifluoromethylphenyl)propanol
carbamate
The title compound was synthesized in a similar
manner to that of Example VIII, except that (R)-3-acetoxy-
2-(o-trifluoromethyl phenyl) propanol, instead of (R)-3-
acetoxy-2-phenyl propanol, was used as a starting
material. Yield 63.1 %. Purity 99.6 %.
[a] _ + 32.5 ° (0.50 in methanol)
WO 96109283 _ 217 b 9 6 0 PCT/KR95100114
EXAMPLE XI
(S)-3-Acetoxy-2-(o-methylphenyl)propanol carbamate
The title compound was synthesized in a similar
manner to that of Example VIII, except that (R)-3-acetoxy-
5 2-(o-methylphenyl) propanol, instead of (R)-3-acetoxy-2-
phenyl propanol, was used as a starting material. Yield
78.7 %. Purity 98.5 %.
[a] _ + 8.3 ' (0.50 in methanol)
EXAMPLE XII
10 (S)-3-Acetoxy-2-(o-thiomethylphenyl) propanol carbamate
The title compound was synthesized in a similar
manner to that of Example VIII, except that (R)-3-acetoxy
2-(o-thiomethylphenyl) propanol, instead of (R)-3-acetoxy
2-phenyl propanol, was used as a starting material. Yield
15 60.3 %. Purity 99.4 %.
[a] _ + 21.9 ' (0.50 in methanol)
EXAMPLE XIII
(S)-3-Acetoxy-2-(2,4-dicholrophenyl) propanol carbamate
Except that (R)-3-acetoxy-2-(2,4-dichlorophenyl)
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propanol, instead of (R)-3-acetoxy-2-phenyl propanol, was
used as a starting material,-Example VIII was repeated to
give the title compound. Yield 67.5 $. Purity 99.7 ~.
[a] _ + 21.7 ° (0.50 in methanol)
EXAMPLE XIV
(S)-3-Acetoxy-2-(2,4-dimethoxyphenyl) propanol carbamate
Except that (R)-3-acetoxy-2-(2,4-dimethoxyphenyl)
propanol, instead of (R)-3-acetoxy-2-phenyl propanol, was
used as a starting material, Example VIII was repeated
to give the title compound. Yield 63.0 ~. Purity 99.1 ~.
[a] _ + 12.4 ' (0.50 inmethanol)
EXAMPLE XV
(S)-2-(2-pyridyl)-1,3-propanediol monocarbamate
In a well dried 250 mL flask, 1.0 g of (S)-3-acetoxy-
2-(2-pyridyl)propanol carbamate obtained in Example I was
placed with 200 mL of 0.05 M phosphate buffer solution (pH
7) and 1.1 g of PLE-A and then, the resulting mixture was
vigorously stirred at a roomtemperature for five hours.
Subsequently, 200 mL of ethyl acetate was added to the
well stirred mixture, for solvent extraction. This
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extraction was repeated three times.
The ethyl acetate solution obtained was dried over
anhydrous magnesium sulfate. A rotary evaporator was used
to remove extra ethyl acetate. Isolation by column
chromatography gave (S)-2-(2-pyridyi)-1,3-propanediol
monocarbamate: Yield 60.0 %. Purity 99.5 %.
Physical properties of (S)-2-(2-pyridyl)-1,3-
propanediol carbamate: [a] _ + 24.1 ' (0.30 in acetone)
iH-NMR (CDC13, 200 MHz), ppm (b): 3.21(s, 1H),
3.66(m, 2H), 4.30(m,2H), 6.43(br, 2H), 7.31(m, 2H),
7.76(m, 1H), 8.53(d, 1H)
EBAMPLE XVI
(S)-2-(2-(3-Chloro)pyridyl)-1,3-propanediol monocarbamate
Except for using (S)-3-acetoxy-2-(2-(3-
cholro)pyridyl)propanol carbamate, instead of (S)-3-
acetoxy-2-(2-pyridyl.)propanol carbamate, as a starting
material, Example XV was repeated to give the title
compound: Yield 57.3 %. Purity 99.8 %.
[a] = t 27.8 ' (0.5D in methanol)
EXAMPLE XViI
(S)-2-(2-(3-Trifluoromethyl)pyridyl)-1,3-propanediol
monocarbamate
WO 96109283 217 6 9 b 0 PCT~S/0012d
' ! ~ a
18
Except for using (S)-3-acetoxy-2-(2-(3-
trifluoromethyl)pyridyl)propanol carbamate, instead of
(S)-3-acetoxy-2-(2-pyridyi)propanol carbamate, as a
starting material, Example XV was repeated to give the
S title compound: Yield 63.2 %. Purity 99.3 %.
(a] _ + 3.5 ° (0.50 in methanol)
EXAMPLE XVIII
(S)-2-(2-(3-Methyl)pyridyl)-1,3-propanediol monocarbamate
Except for using (S)-3-acetoxy-2-(2-(3-
methyl)pyridyl)propanol carbamate, instead of (S)-3-
acetoxy-2-(2-pyridyl)propanol carbamate, as a starting
material, Example XV was repeated .to give the title
compound: Yield 72.8 %. Purity 98.7 %.
[a] _ + 8.7 ' (0.50 in methanol)
EXAMPLE XIX
(S)-2-(2-(3-Thiomethyl)pyridyl)-1,3-propanediol
monocarbamate
Except for using (S)-3-acetoxy-2-(2-(3-
thiomethyl)pyridyl)propanoi carbamate, instead of (S)-3-
acetoxy-2-(2-pyridyl)propanol carbamate, as a starting
material, Example.XV was repeated to give the title
WO 96109283 F 217 6 9 6 Q PCT~5100124
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compound: Yield 67.5 %. Purity 99.5 %.
' [a] _ + 20.4 ° (0.50 in methanol)
EXAMPLE XX
(S)-Z-(2-(4,6-dichloro)pyridyl)-1,3-propanediol
monocarbamate
The title compound was synthesized in a similar
manner to that of Example XV, except that (S)-3-acetoxy-2-
(2-(4,6-dichloro)pyridyl)propanol carbamate, instead of
(S)-3-acetoxy-2-(2-pyridyl)propanol carbamate, was used
as a starting material. Yield 60.5 %. Purity 99.5 %.
[a] _ + 33.1 ' (0.50 in methanol)
EXAMPLE XXI
(S)-2-(2-(4,6-dimethoxy)pyridyl)-1,3-propanediol
monocarbamate
The title compound was synthesized in a similar
manner to that of Example XV, except that (S)-3-acetoxy-2-
(2-(4,6-dimethoxy)pyridyl)propanol carbamate, instead of
(S)-3-acetoxy-2-(2-pyridyl) propanol carbamate, was used
as a starting material. Yield 70.4 %. Purity 99.5 %.
[a] _ + 11.8 ° (0.50 in methanol)
WO 96109283 G, .:.:. 217 6 9 6 p P'T'~'~S~oorz~ ~
EXAMPLE XXII
(S)-2-Phenyl-1,3-propanediol monocarbamate
In a 500 mL flask equipped with a magnetic stirrer,
2.37 g of (S)-3-acetoxy-2-phenylpropanol carbamate (0.01
5 mole) obtained in Example VIII was placed and 200 mL of
phosphate buffer solution (0.014 mole, pH 7) and 1.2 g of
PLE-A were added. The reaction mixture was stirred at
room temperature.
When the conversion rate of (S)-3-acetoxy-2
10 phenylpropanol carbamate reached 90 %, which was detected
by HPLC, the reaction was stopped and the resulting
mixture was filtered. The filtrate was extracted three
times with ethyl acetate, to isolate an organic layer of
which the extra solvent was then distilled off by a rotary
I5 evaporator. Isolation by column chromatography using a
mixture of ethyl acetate and n-hexane (1:1) as the mobile
phase gave (S)-2-phenyl-1,3-propanediol monocarbamate:
Yield 70.1 %. Purity 99.7 %.
Physical properties of (S)-2-phenyl-1,3-propanediol
20 monocarbamate: [c] = f 1.8 ' (0.03 in ethanol)
1H-NMR (CDC13, 200 MHz), ppm (b): 2.49-2.63(m, 1H),
2.95-3.21(m, IH), 3.75-3.88(m, ZH), 4.37(d, 2H), 4.91(b,
2H), 7.21-7.36(m, 5H)
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EXAMPLE XXIII
v
(S)-2-(o-Chlorophenyl)-1,3-propanediol monocarbamate
The title compound was synthesized in a similar
manner to that of Example XXII, except that (S)-3-acetoxy-
2-(o-cholrophenyl)propanol carbamate, instead of (S)-3-
acetoxy-2-phenylpropanol carbamate, was used as a starting
material. Yield 76.3 %. Purity 99.3 %.
[a] _ + 8.7 ' (0.50 in methanol)
EXAMPLE XXIV
(S)-2-(o-Trifluoromethylphenyl)-1,3-propanediol
monocarbamate
The title compound was synthesized in a similar
manner to that of Example XXII, except that (S)-3-acetoxy-
2-(o-trifluoromethylphenyl)propanol carbamate, instead of
(S)-3-acetoxy-2-phenylpropanoi carbamate, was used as a
starting material. Yield 63.5 %. Purity 99.4 %.
[Q] _ + 21.3 ' (0.50 in methanol)
EXAMPLE XXV
(S)-2-(o-methylphenyl)-1,3-propanediol monocarbamate
WO 9Gl09283 217 6 9 6 fl PCT/KR95/00124
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The title compound was synthesized in a similar
manner to that of Example XXII, except that (S)-3-acetoxy-
2-(o-methylphenyl)propanol carbamate, instead of (S)-3-
acetoxy-2-phenylpropanol carbamate, was used as a starting
material. Yield 78.3 %. Purity 99.0 %.
[a] = t 5.2 ' (0.50 in methanol)
EXAMPLE XXVI
(S)-2-(o-Thiomethylphenyl)-1,3-propanediol monocarbamate
The title compound was synthesized in a similar
manner to that of Example XXII, except that (S)-3-acetoxy-
2-(o-thiomethyiphenyl)propanol carbamate, instead of (S)-
3-acetoxy-2-phenylpropanol carbamate, was used as a
starting material. Yield 75.7 %. Purity 98.7 %.
[a] _ + 18.2 ' (0.50 in methanol)
EXAMPLE XXVII
(S)-2-(2,4-Dichlorophenyl)-1,3-propanediol monocarbamate
The title compound was synthesized in a similar
manner to that of Example XXII, except that (S)-3-acetoxy-
2-(2,4-dichlorophenyl)propanol carbamate, instead of (S)-
3-acetoxy-2-phenylpropanol carbamate, was used as a
starting material. Yield 78.9 %. Purity 99.7 %.
W096109283 " - PCTlKR95100124
X176960
23
[a] _ + 18.0 ' (0.50 in methanol)
EXAMPLE XXVIII
(S)-2-(2,4-dimethoxyphenyl)-1,3-propanediol monocarbamate
The title compound was synthesized in a similar
manner to that of Example XXII, except that (S)-3-acetoxy-
2-(2,4-dimethoxyphenyl)propanol carbamate, instead of (S)-
3-acetoxy-2-phenylpropanol carbamate, was used as a
starting material. Yield 65.3 ~. Purity 99.2 ~.
[a] _ + 25.1 ' (0.50 in methanol)
Other features, advantages and embodiments of the
present invention disclosed herein will be readily
apparent to those exercising ordinary skill after reading
the foregoing disclosures. In this regard, while specific
embodiments of the invention have been described in
considerable detail, variations and modifications of these
embodiments can be effected without departing from the
spirit and scope of the invention as described and
claimed.
