醋酸巴多昔芬的合成工艺改进

An Improved Process for Synthesis of Bazedoxifene Acetate

目的:改进醋酸巴多昔芬的合成工艺。方法:以对羟基苄醇和环己亚胺基乙基氯盐酸盐为起始原料,经过亲核取代、氯代得到侧链,4-苄氧基苯丙酮和4-苄氧基苯肼盐酸盐经缩合得母核,侧链和母核缩合后,经成盐,氢解、中和,与乙酸成盐总计6步得目标化合物。结果:目标化合物经质谱、核磁共振确证其结构。总收率可达53%,产品高效液相色谱法(HPLC)获得纯度可达99.5%以上。结论:改进后的工艺步骤大大缩短,且操作简单,醋酸巴多昔芬收率和纯度较高,适合工业化生产。

Objective： To improve the synthetic process of bazedoxifene acetate.Methods：The side chain was synthesized from 4-hydroxybenzyl alcohol and 2-（ hexamethyleneimino） ethyl chloride hydrochloride as starting materials through nucleophilic substit-uent and chlorination.The stemnucleus was obtained by condensation taking 4-benzyloxypropiophenone and 4-methoxyphenyl-hydrazine hydrochloride as raw materials; the side chain and the stemnucleus were condensed and process by acidification,hydro-genolysis,neutralization and acidification with acetic acid to get the target compound via total six steps.Results： The structure of the target compound was confirmed by ESI-MS and 1H-NMR.The total yield was 53%,and the High Performance Liquid Chromatogra-phy （HPLC） purity was more than 99.5%.Conclusion：The improved process of bazedoxifene acetate with short steps, simple op-eration,good yield and purity is feasible for industralization.