盐酸他喷他多的合成

Synthesis of Tapentadol Hydrochloride

1-(3-甲氧基苯基)-1-丙酮与N,N-二甲基氯甲胺经烃化及手性拆分得到(S)-3-(二甲胺基)-1-(3-甲氧基苯基)-2-甲基丙酮,与乙基膦酸二乙酯经Horner-Emmons-Wittig反应及催化氢化制得(2R,3R)-3-(3-甲氧基苯基)-N,N,2-三甲基戊胺,最后经脱甲基、成盐酸盐得到盐酸他喷他多,总收率约51%。

Tapentadol hydrochloride was synthesized from 1-（3-methoxyphenyl）-l-propanone and N,N- dimethyl-chloromethylamine by alkylation and chiral resolution to give （S）-3-dimethylamino-1-（3-methoxyphenyl）-2- methylpropanone, which was subjected to Homer-Emmons-Wittig reaction with diethyl ethy｜phosphonate and catalytic reduction to give （2R,3R）-3-（3-methoxyphenyl）-N,N,2-trimethylpentanamine, followed by demethylation and salt formation with an overall yield of about 51%.