Preparation method of (2R,3R)-3-(3-methoxyphenyl)-N,N,2-trimethylpentylamine hydrochloride as intermediate of analgesic tapentadol.

Abstract

The invention relates to the method for prepg. (2R,3R)-3-(3-methoxyphenyl)-N,N,2-trimethylpentylamine hydrochloride, which is used as intermediate of analgesic tapentadol. (2R,3R)-3-(3-Methoxyphenyl)-N,N,2-trimethylpentylamine hydrochloride was prepd. via chlorination of (2S,3R)-1-(dimethylamino)-3-(3-methoxyphenyl)-2-methylpentan-3-ol; the resulting (2S,3R)-1-(dimethylamino)-3-chloro-3-(3-methoxyphenyl)-2-methylpentane underwent salt formation to give the corresponding HCl salt, which underwent stereoselective hydrogenolysis catalyzed by 5-10% Pd/C or Raney nickel to give (2R,3R)-3-(3-methoxyphenyl)-N,N,2-trimethylpentylamine, which underwent salt formation to give the title compd. This invention has the advantages of sanitation, safety, convenient post-treatment, low prodn. cost, and shortened reaction time. [on SciFinder(R)]