Process for the preparation of tapentadol

摘要

Disclosed herein is an improved process for the preparation of 3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol of Formula-I and its pharmaceutically acceptable salt which comprises the reaction of (S)-1-(dimethylamino)-2-methylpentan-3-one of formula VIII with 3-bromo anisole of formula II under Grignard conditions to get the compound (2S,3R)-1-(dimethylamino)-3-(3-methoxyphenyl)-2-methyl pentan-3-ol of formula V followed by activation of the —OH group of the formula V to convert into sulfonate esters of formula IX, which are on reductive deoxygenation to yield (2R,3R)-3-(3-methoxyphenyl)-N,N,2-trimethylpentan-1-amine of formula VII and demethylation of formula VII to obtain the compound 3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol of Formula-1.

主权项

1. A process for the preparation of 3-[(R2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol of Formula-I or its pharmaceutically acceptable salt, said process comprising:a) reacting (S)-1-(dimethylamino)-2-methylpentan-3-one of Formula-VIII with 3-bromo anisole of Formula-II under Grignard reaction conditions to obtain the compound (2S,3R)-1-(dimethylamino)-3-(3-methoxyphenyl)-2-methyl pentan-3-ol of Formula-V; andb) activating the —OH group of (2S,3R)-1-(dimethylamino)-3-(3-methoxyphenyl)-2-methyl pentan-3-ol with methanesulfonic acid or para-toluenesulfonic acid in the presence of a solvent and a mineral acid to obtainan activated compound of Formula IX where R=−SO2CH3 or R=—SO2C5H4CH3; andc) demethylating the activated compound to obtain 3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol of Formula-I.