Invention Grant
US07709662B2 Method of manufacturing (S)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine hydrochloride (duloxetine) 有权
制备(S)-N-甲基-3-(1-萘氧基)-3-(2-噻吩基)丙胺盐酸盐(度洛西汀)的方法

Method of manufacturing (S)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine hydrochloride (duloxetine)
Abstract:
A method of preparation of (S)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine of formula (I) or its pharmaceutically acceptable salt, in which (RS)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine of formula (III) is reacted with an optically active acid, after which a crystallization is made of that diastereoisomer which yields, by reaction with an inorganic or organic base, (S)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine of formula (S)-III, which is then demethylated using alkylchloroformates, followed by a hydrolysis and optional conversion of the compound of formula (I) to its salt.
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