An improved and scalable synthesis of zolpidem via a CuI/BINOL-mediated tandem reaction of imine and alkyne

Heterocyclic communications

article

Bingbing Zhang¹  Guangsheng Shan¹  Qiaoning Ma¹  Qianqian Xu¹  Xinsheng Lei¹ 

[1] School of Pharmacy, Fudan University

关键词: copper;    heterocycles;    hypnotic;    tandem reaction;    zolpidem;   

DOI  :  10.1515/hc-2017-0152

学科分类：内科医学

来源: De Gruyter

【 摘 要 】

An improved and scalable method for the synthesis of zolpidem ( 1 ), a hypnotic drug, was developed. A two-step sequence involving imine formation and subsequent tandem reaction between an imine and propiolamide in the presence of CuI/BINOL, an efficient promoter for the tandem reaction, is described. Zolpidem was efficiently prepared in a 54% isolated yield and the hemitartrate salt of zolpidem was produced in 37% yield by simple crystallization, without tedious column chromatography. The procedure can be scaled up to >10 g. The yield of 1 increased to 83% following isolation of the intermediate imine 5 .

【 授权许可】

CC BY|CC BY-NC-ND