1-phenylpyrrolidone derivatives having optical activity, intermediate for the preparation thereof and processes for their preparation
AssigneeTaiho Pharmaceutical Co., Ltd.
InventorsShingo Yano, Tomoyasu Ohno, Kazuo Ogawa, Tetsuhiko Shirasaka
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Abstract
Disclosed are a 1-phenylpyrrolidone derivative having optical activity and represented by the formula (I) ##STR1## wherein R represents an optionally substituted optically active .alpha.-phenylethylamino group, a 1-phenylpyrrolidone derivative represented by the formula (I-a) ##STR2## and processes for preparing the 1-phenylpyrrolidone derivatives represented by the formulas (I) and (I-a), respectively.
Claims23
A 1-phenylpyrrolidone derivative having optical activity and represented by the formula (I) ##STR12## wherein R represents an optionally substituted optically active .alpha.-phenylethylamino group.
A 1-phenylpyrrolidone derivative represented by the formula (I-a) ##STR15##
A process for preparing a 1-phenylpyrrolidone derivative having optical activity and represented by the formula (I) ##STR16## wherein R represents an optionally substituted optically active .alpha.-phenylethylamino group, characterized in that the process comprises the steps of:
- a) reacting a compound represented by the formula (I-a) ##STR17## with a chlorinating agent in a solvent which does not participate in the reaction to convert the compound to the acid chloride thereof,
- b) reacting the acid chloride prepared in step i) with an optionally 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) ##STR18## wherein R is as defined above, and c) optionally conducting resolution of the diastereomer mixture obtained in step ii) to give an optically active compound represented by the formula (I-b') ##STR19## wherein R is as defined above.
A process for preparing a compound represented by the formula (I-a) ##STR22## comprising the step of react a racemic mixture represented by the formula (III) ##STR23## with phthalic anhydride for esterification in the presence of a basic compound in a solvent which does not adversely affect the reaction.
A process for preparing an optically active 1-phenylpyrrolidone derivative of the formula (I):
- ##STR24## wherein R is a substituted or unsubstituted optically active .alpha.-phenylethylamino group, comprising the steps of:
- a) esterifying a racemic mixture of the formula (III):
- ##STR25## with phthalic anhydride in the presence of a basic compound in a solvent which does not adversely affect the reaction to produce a compound of the formula (I-a):
- ##STR26## b) reacting the compound of formula (I-a) produced in step a) with a chlorinating agent in a solvent which does not participate in the reaction, to produce the acid chloride of compound (I-a), and
- c) reacting the acid chloride produced in step b) with a substituted or unsubstituted optically active .alpha.-phenylethylamine in the presence of a basic compound in a solvent which does not participate in the reaction, to produce a mixture of diastereomers of the compound of formula (I).
(S)-(+)-4-[1-(4-t-Butylphenyl)-2-pyrrolidone-4-yl]methoxybenzoic acid, or a lower alkyl ester thereof, represented by the formula (II) ##STR27## wherein R' is a hydrogen atom or a lower alkyl group.
Methyl (S)-(+)-4-[1-(4-t-butylphenyl)-2-pyrrolidone-4-yl]methoxybenzoate.
(S)-(+)-4-[1-(4-t-Butylphenyl)-2-pyrrolidone-4-yl ]methoxybenzoic acid.
A method for treating hyperlipidemia in a patient comprising administering (S)-4-[1-(4-t-butylphenyl)-2-pyrrolidone-4-yl]methoxybenzoic acid, or a lower alkyl ester thereof, represented by the formula (II) ##STR28## wherein R' is a hydrogen atom or a lower alkyl group.
Dependencies are inferred from the claim text.