[EN] PROCESS FOR THE PREPARATION OF TAPENTADOL<br/>[FR] PROCÉDÉ DE PRÉPARATION DE TAPENTADOL
申请人:INDOCO REMEDIES LTD
公开号:WO2012023147A1
公开(公告)日:2012-02-23
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.
本文揭示了一种改进的制备3-[(2R,3R)-1-(二甲氨基)-2-甲基戊-3-基]苯酚式-I及其药用可接受盐的过程,该过程包括将式VIII的(S)-1-(二甲氨基)-2-甲基戊-3-酮与式II的3-溴苯甲醚在Grignard条件下反应,得到化合物(2S,3R)-1-(二甲氨基)-3-(3-甲氧基苯基)-2-甲基戊-3-醇式V,然后激活式V的-OH基团,转化为式IX的磺酸酯,再通过还原脱氧作用得到化合物(2R,3R)-3-(3-甲氧基苯基)-N,N,2-三甲基戊-1-胺式VII,最后通过去甲基化反应得到化合物3-[(2R,3R)-1-(二甲氨基)-2-甲基戊-3-基]苯酚式-I。