op500386g_si_001.pdf (369.06 kB)
A Novel and Practical Synthesis of Ramelteon
journal contribution
posted on 2015-02-20, 00:00 authored by Sa Xiao, Chao Chen, Hongyan Li, Kuaile Lin, Weicheng ZhouAn 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.