A Novel and Practical Synthesis of Ramelteon

An efficient and practical process for the synthesis of ramelteon <b>1</b>, 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-8<i>H</i>-indeno­[5,4-<i>b</i>]­furan-8-one <b>2</b> and the subsequent hydrogenation which successfully implement four processes (debromination, dehydration, olefin reduction, and cyano reduction) into one step to produce the ethylamine compound <b>13</b> 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 <b>1</b> is easily obtained from <b>13</b> 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 <b>2</b>.