醋酸巴多昔芬的合成

Synthesis of bazedoxifene acetate

目的:合成骨质疏松治疗药物醋酸巴多昔芬。方法:以对羟基苯甲醛、2-(环己亚胺基)乙基氯盐酸盐为起始原料,经缩合、还原、氯代三步得侧链;以对羟基苯丙酮为起始原料,经缩合、溴代、缩合、环合四步得母核;侧链与母核缩合后,再经氢解、成盐得醋酸巴多昔芬,总计10步反应合成目标产物。结果:目标化合物经MS和1H-NMR确证结构,总收率18.1%。结论:本研究路线反应条件温和,操作简单,适合于工业化生产。

Objective：To synthesize osteoporosis therapeutic agent bazedoxifene acetate. Methods： Baze- doxifene acetate was synthesized via ten steps. The side chain was got by condensation, reduction and chlorination starting from p-hydroxybenzaldehyde and 2-（hexamethyleneimino） ethyl chloride hydrochloride. The parent nucleus was obtained by condensation, bromination, condensation and cyclization taking p-hydroxypropiophenone as raw material. The obtained side chain and parent nucleus were condensed and processed by hydrogenolysis and acidifi- cation to get the objective compound. Results： The chemical structure of the target compound was confirmed by MS and 1H-NMR. The total yield was 18.1%. Conclusion： This synthetic process is mild and simple, which is feasi- ble for industrialization.