三光气法合成盐酸甲哌卡因的工艺改进

Improved synthesis of mepivacaine hydrochloride by triphosgene

目的研究三光气法合成盐酸甲哌卡因。方法以三光气为氯化试剂,NaOH为N-甲基化缚酸剂,2-哌啶甲酸经酰氯化、酰胺化、N-甲基化、成盐得盐酸甲哌卡因。结果合成盐酸甲哌卡因总收率为68.1%,中间体N-(2,6-二甲苯基)-2-哌啶甲酰胺的收率由50.1%提高到73.9%,N-甲基化收率由90.0%提高到96.0%。结论整个工艺反应条件温和,操作简单,对环境友好。

Objective To determine the synthesis of mepivacaine hydrochloride by triphosgene. Methods Mepivacainehydrochloride was synthesized by chlorination by triphosgene, and amidation, methylation by using NaOH as acid binding agent, and acidification from the acid. Results The overall yield was 68.1%, and the yield of N-pipecolic acid-2, 6-xylidide was improved from 50.1% to 73.9% and meanwhile that of methylation was increased from 90. 0% to 96.0%. Conclusion The process is mild, simply handled and environment friendly.