| 摘要 |
A method for preparing clopidogrel hydrogensulfate having dextrorotatory optical activity is provided to improve purity, efficiency and yield of preparation by using a novel intermediate represented by the formula(2), so that the prepared clopidogrel hydrogensulfate is useful for inhibition of platelet coagulation and thrombosis. A method for preparing the clopidogrel hydrogensulfate, (+)-(S)-alpha-(2-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridinyl-5-methyl acetate represented by the formula(1) or pharmaceutically acceptable salts thereof comprises the steps of: reacting (R)-2-hydroxy-2-(2-chlorophenyl) acetate with chlorophosphonium ion represented by the formula(3) at -10 to 5 deg. C to prepare (R)-2-chloro mandelic acid phosphonium ester derivatives represented by the formula(2), in which R is hydrogen atom or C1-C4 alkyl group; X is OP(R1)3; R1 is C1-C4 alkyl group, aromatic ring compound such as phenyl, or substituted aromatic ring compounds such as 4-nitrophenyl, 4-methoxyphenyl or 4-chlorophenyl group; and reacting the compounds represented by the formula(2) with 4,5,6,7-tetrahydrothieno[3,2-c]pyridine at 20-90 deg. C for 1-5 hours.
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