Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1994-05-03
1995-12-12
Springer, David B.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C07D20726, A61K 3140
Patent
active
054751187
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a novel 1-phenylpyrrolidone derivative having optical activity, an intermediate for the preparation of the derivative, and processes for their preparation. The compound of the present invention is useful as an intermediate for preparing an optically active form of a compound represented by the following formula (II) which is useful as an agent for treating hyperlipidemia which has an activity to inhibit the synthesis of fatty acids and an activity to inhibit the synthesis of cholesterol ##STR3## wherein R' is a hydrogen atom or a lower alkyl group such as an alkyl group having 1 to 6 carbon atoms.
BACKGROUND ART
An optically inactive, racemic form of the compound of the formula (II) is disclosed in Japanese Unexamined Patent Publication (Kokai) Hei 3-275666 (European Patent Publication No. 393607), but no report has been made on the synthesis of an optically active form of the compound of the formula (II).
DISCLOSURE OF THE INVENTION
The present inventors conducted extensive research on processes for preparing the optically active form of the compound of the formula (II) and found that a 1-phenylpyrrolidone derivative having optical activity and represented by the formula (I) which is a novel compound undisclosed in literature is useful as an intermediate for preparing the optically active form of the compound of the formula (II). The present inventors completed this invention on the basis of this finding.
The present invention provides a 1-phenylpyrrolidone derivative having optical activity and represented by the formula (I) ##STR4## wherein R represents an optionally substituted optically active .alpha.-phenylethylamino group.
The present invention also provides a 1-phenylpyrrolidone derivative represented by the formula (I-a) ##STR5## which is an intermediate for preparing the 1-phenylpyrrolidone derivative of the formula (I) having optical activity.
The present invention further provides a process for preparing the foregoing 1-phenylpyrrolidone derivative having optical activity and represented by the formula (I), characterized in that the process comprises the steps of: agent in a solvent which does not participate in the reaction to convert the compound to the acid chloride thereof, substituted optically active .alpha.-phenylethylamine in the presence of a basic compound in a solvent which does not participate in the reaction to give a mixture of diastereomers of a compound represented by the formula (I-b) ##STR6## wherein R is as defined above, and iii) optionally conducting resolution of the diastereomer mixture obtained in the step ii) to give an optically active compound represented by the formula (I-b') ##STR7## wherein R is as defined above.
The present invention also provides a process for preparing the foregoing compound of the formula (I-a), comprising the step of reacting a racemic mixture represented by the formula (III) ##STR8## with phthalic anhydride for esterification in the presence of a basic compound in a solvent which does not adversely affect the reaction.
The optically active 1-phenylpyrrolidone derivatives of the formula (I) may exist as four different optical isomers. The present invention includes each of such optically active isomers, and any mixtures of the diastereomers (optically active isomers).
The substituent for the "optionally substituted optically active .alpha.-phenylethylamino group" which is represented by R in the invention is one introduced to the o-position, m-position or p-position of the phenyl group of the .alpha.-phenylethylamino group. Particularly preferable among them is one introduced to the p-position thereof. Examples of the substituent are a lower alkyl group having 1 to 4 carbon atoms, a halogen atom such as fluorine, chlorine, bromine, iodine, etc., nitro group, and so on. Preferred p-substituted phenyl groups are p-tolyl group, p-bromophenyl group, p-nitrophenyl group, etc.
The optically active 1-phenylpyrrolidone derivative of the formula (I) of the invention (I-b, I-b') can be synth
REFERENCES:
patent: 5145865 (1992-09-01), Fuji et al.
Jacques et al, "Enantiomers, Racemates, and Resolutions", 1991, pp. 263-264.
Ogawa Kazuo
Ohno Tomoyasu
Shirasaka Tetsuhiko
Yano Shingo
Springer David B.
Taiho Pharmaceutical Co. Ltd.
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