First practical resolution of a 3-(4-methoxyphenyl)glycidic acid ester by preferential crystallization and synthesis of diltiazem

摘要

Among the various esters of 3-(4-methoxyphenyl)glycidic acid, 4-chloro-3-methylphenyl ester (+/-)-3 was found to exist as a conglomerate, and could be alternately resolved into (+)- and (-)-3 of >98% ee by a preferential crystallization procedure. Furthermore, a 1,5-benzothiazepine derivative, (+)-6, a significant intermediate of diltiazem, was prepared in one pot in 76% overall yield through the treatment of enantiomerically pure (-)-3 with 2-aminothiophenol followed by a ring closing reaction. (C) 1998 Elsevier Science Ltd. All rights reserved. [References: 26]