A Practical Procedure for the Large-Scale Preparation of Methyl (2R,3S)-3-(4-Methoxyphenyl)glycidate, a Key Intermediate for Diltiazem

Citations Over TimeTop 18% of 2002 papers

Abstract

A practical synthesis of methyl (2R,3S)-3-(4-methoxyphenyl)glycidate (-)-2, a key intermediate for diltiazem (1), was developed. Treatment of methyl (E)-4-methoxycinnamate 3 with chiral dioxirane, generated from chiral ketone 4, provided (-)-2 in 77% ee and 89% yield. The crude mixture of (-)-2 and 4 was efficiently separated by the use of novel and simple equipment performing a lipase-catalyzed transesterification and a continuous dissolution and crystallization to furnish the optically pure (-)-2 and recovery of 4 in 74% and 91% yield, respectively.

Related Papers

• → Lethal Diltiazem Poisoning(2002)17 cited
• → Overdose of diltiazem(1994)3 cited
• Effect of calcium channel blocker (diltiazem) on platelet aggregation.(1991)
• Girona perd posicions: productivitat, competitivitat i nivell de vida(1992)
• [A comparison between diltiazem SR and diltiazem HCL in the treatment of angina pectoris].(1993)