| 摘要 |
A method for preparing S-(+)-clopidogrel is provided to conveniently obtain the S-(+)-clopidogrel with high optical purity and chemical purify by forming a diastereomeric salt from a racemic carboxylic acid intermediate of clopidogrel using (+)-cinchonine, and then optically-resoluting it using an adequate solvent. The method comprises the steps of: (a) reacting a racemic carboxylic acid of clopidogrel represented by the formula(2a) with (+)-cinchonine represented by the formula(3) so as to prepare a diastereomeric salt represented by the formula(4); (b) reacting the diastereomeric salt under the acidic condition to prepare a carboxylic acid of S-(+)-clopidogrel represented by the formula(2b); and (c) reacting the carboxylic acid of the formula(2b) with methanol under the acidic condition to prepare S-(+)-clopidogrel represented by the formula(1). In the method, the carboxylic acid of S-(+)-clopidogrel is optically resoluted at a temperature of -30 to 60 deg.C through extraction using a solvent selected from the group consisting of water, ketone, alcohol, ether, amide, ester, hydrocarbon, chlorohydrocarbon, nitrile and mixtures thereof.
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