A novel synthesis of a key intermediate for diltiazem

A practical synthesis of methyl (2R,3S)-3-(4-methoxyphenyl)glycidate (-)-2a , a key intermediate for diltiazem (3), was described. Treatment of methyl (E)-4-methoxycinnaniate (E)-1a with chiral dioxirane, generated in situ fro m a catalytic amount of an 11-membered C-2-symmetric binaplithyl ketone 7a. provided (-)-2a in 78% ee and 89% yield. The crude mixture of (-)-2a and 7 a was efficiently separated by the use of novel equipment performing contin uous dissolution and crystallization to furnish the optically pure (-)-2a ( >99% ee) and recovery of 7a in 64 and 88% yields, respectively. (C) 2001 El sevier Science Ltd. All rights reserved.