盐酸罗哌卡因的合成工艺研究

Research on synthetic technology of ropivacaine hydrochloride

目的探讨盐酸罗哌卡因的合成方法。方法本研究以2-哌啶甲酸为起始原料,与2,6-二甲基苯胺进行酰胺化反应得到N-(2,6-二甲基苯)-2-哌啶甲酰胺,与溴代正丙烷进行取代反应得到N-(2,6-二甲基苯基)-1-正丙基哌啶-2-甲酰胺,再通过与D-酒石酸在有机溶剂中拆分反应即可制得盐酸罗哌卡因。结果所得盐酸罗哌卡因的光学纯度在99.5%以上,总收率约25%。结论本方法操作简便,所得产品光学纯度高,适合于药用,具有一定的商业化价值。

Objective To explore the synthetic method of ropivacaine hydrochloride. Methods 2-piperidinecarboxylic acid was starting material. N-（2, 6-dimethylphenyl）-2-pppiperidine amide was obtained by amidation reaction of 2-piperidinecarboxylic acid and 2, 6-dimethylaniline. N-（2, 6-dimethylphenyl）-1- n-propyl-2-piperidine formamide was obtained by substitution reaction of 1-bromopropane and N-（2, 6-dimethylphenyl）-2-pppiperidine amide. Then ropivacaine hydrochloride was obtained by resolution reaction in organic solvent of N-（2, 6-dimethylphenyl）-1- n-propyl-2-piperidine formamide and D-tartrate. Results Optical purity of the obtained ropivacaine hydrochloride was over 99.5% and total yield was about 25%. Conclusion This method is simple and convenient and the obtained products were of high optical purity. It is suitable for medicinal purposes, with certain commercial value.