A Novel and Practical Synthesis of Ramelteon

作者：Xiao Sa; Chen Chao; Li Hongyan; Lin Kuaile; Zhou Weicheng^*

来源：Organic Process Research & Development, 2015, 19(2): 373-377.

DOI：10.1021/op500386g

An efficient and practical process for the synthesis of ramelteon 1, a sedative-hypnotic, is described. Highlights in this synthesis are the usage of acetonitrile as nucleophilic reagent to add to 4,5-dibromo-1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-one 2 and the subsequent hydrogenation which successfully implement four processes (debromination, dehydration, olefin reduction, and cyano reduction) into one step to produce the ethylamine compound 13 where dibenzoyl-l-tartaric acid is selected both as an acid to form the salt in the end of hydrogenation and as the resolution agent. Then, target compound 1 is easily obtained from 13 via propionylation. The overall yield in this novel and concise process is almost twice as much as those in the known routes, calculated on compound 2.

• 出版日期2015-2
• 单位上海医药工业研究院