文献类型：期刊文献

中文题名：拉科酰胺的合成工艺改进

英文题名：Process Improvement on the Synthesis of Lacosamide

作者：陈一芬[1];王超[1];禹艳坤[1];冀亚飞[1]

机构：[1]华东理工大学药学院,上海200237

年份：2010

卷号：18

期号：4

起止页码：520

中文期刊名：合成化学

外文期刊名：Chinese Journal of Synthetic Chemistry

收录：CSTPCD;;北大核心:【北大核心2008】；CSCD:【CSCD_E2011_2012】；

语种：中文

中文关键词：拉科酰胺;抗癫痫药;O-甲基化;酰胺化;药物合成;工艺改进

外文关键词：Lacosamide; anticonvulsant drug; O-methylation; amidation; drug synthesis; process improvement

摘要：以N-Boc-D-丝氨酸为起始原料,经羟基甲基化、与苄胺的酰胺化、脱除Boc保护基和胺基乙酰化4步反应合成了拉科酰胺(1),总收率76.0%,其结构经1H NMR和MS表征。在关键中间体(R)-N-苄基-2-N-Boc-氨基-3-甲氧基丙酰胺的合成中,以三乙胺代替N-甲基吗啉作为缚酸剂,以氯甲酸异丙酯代替DCC为缩合剂,有效降低了合成成本。
Lacosamide was synthesized by a four-step reaction of methylation hydroxyl,the amidation of benzylamine,the deprotecting Boc-group and the acetylation from N-Boc-D-serine in total yield of 76.0%.The structure was characterized by 1H NMR and MS.In the synthesis of the key intermediate（R）-N-benzyl-2-N-Boc-amino-3-methoxypropionamide,the amidation was carried out by using triethylamine instead of N-methylmorpholine as the acid-capturing agent and isopropyl chloroformate instead of DCC as the condensing agent to achieve a good cost effective.