拉科酰胺的合成工艺改进  

Process Improvement on the Synthesis of Lacosamide

作　　者：陈一芬[1] 王超[1] 禹艳坤[1] 冀亚飞[1] 

机构地区：[1]华东理工大学药学院,上海200237

出　　处：《合成化学》2010年第4期520-522,共3页Chinese Journal of Synthetic Chemistry

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.

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 

分 类 号：R914.5[医药卫生—药物化学] O623.626[医药卫生—药学]