酒石酸唑吡坦的合成工艺研究

Improved synthesis of zolpidem tartrate

目的寻找催眠药酒石酸唑吡坦的新合成方法。方法以对甲基苯乙酮为起始原料,经氧化反应得到中间体对甲基苯基乙二醛水合物,再经环合反应得到6-甲基-2-(4-甲基苯基)咪唑并[1,2-a]吡啶-3-乙酸,经缩合反应得到N,N,6-三甲基-2-(4-甲基苯基)咪唑并[1,2-a]吡啶-3-乙酰胺,最后与L-(+)-酒石酸成盐得到酒石酸唑吡坦。结果与结论优化后的工艺路线比原工艺缩短3步反应,总收率为27.3%(以对甲基苯乙酮计),产物纯度高达99.8%。酒石酸唑吡坦的结构经MS、^(1)H-NMR谱确证,改进后的工艺路线原料廉价、易得,反应条件温和,后处理简单,成本低,适合工业化生产。

Zolpidem tartrate is a class of sedative-hypnotic drugs that acts on GABA receptor.An improved synthetic process of zolpidem tartrate has been developed in this study.The synthesis of zolpidem tartrate started from 4'-methylacetophenone via oxidation reaction and intermolecular cyclization reaction,followed by condensation with dimethylamine hydrochloride and salt formation.The final zolpidem tartrate was produced with a total yield of 27.3%and HPLC purity of 99.8%.The structure of zolpidem tartrate had been confirmed by MS and^(1)H-NMR.This improved process has several advantages compared with those reported procedures,such as inexpensive materials,low toxicity,milder reaction conditions,simple postprocessing,which is more suitable for industrial production.