异博定合成工艺的研究

Synthesis of Verapamil

对异博定习用生产工艺进行改进,对其中收率较低的氰化和缩合成盐步骤采用相转移催化剂,使氰化步骤中邻二甲氧基苯乙腈(VCI)收率提高到68％,缩合成盐步骤收率提高到35％。文中同时研究出氰化较佳工艺:甲乙酮:甲苯=7％～15％(ν);三乙胺:VCl=1％～3％(m);H_2O:VCl 5％～10％(m);三乙胺:VCl:1∶1.1～1.5(n)。反应温度75～95℃,反应时间2.5～4h。异博定成品总收率为11.3％。

Verapamil was prepared by a new and facile method. Veratryl cyanide was prepared by chloromethylating veratrol in solution in toluene and then reacting the resulting veratryl chloride with from 1.1-1.5 moles of an alkali metal cyanide, from 5 - 10% of water by weight (based on veratryl chloride) ; from 7-15% of a ketone (based on toluene) ; from 1-3% phase transfer catalyst (based on veratryl chloride) was added. The yield of cyanidation was 68% . This paper also present some new method of hydrogenating condensation which can be processed smoothly with good yields. The overall yield of verapamil was 11.3 % .