巴多昔芬的合成工艺改进

Improvement of Synthesis Process of Bazedoxifene

为了改进巴多昔芬的合成工艺,以4-苄氧基苯肼盐酸盐和4-苄氧基苯丙酮为起始原料,经过Fischer吲哚合成法得到母体。吲哚化合物3与侧链缩合后,经水解、取代、还原、氢解6步得到目标化合物。结果表明,目标化合物经质谱、核磁共振确证其结构。总产率可达44%,产品HPLC法获得纯度可达99.3%以上。改进后的工艺反应条件温和,步骤大大缩短,副产物很少,后处理简单,适合工业化生产。

To improve the synthetic process of bazedoxifene, the stemnucleus was obtained by fischer indole synthesis taking 4-methoxyphenylhydrazine hydrochloride and 4-benzyloxypropiophenone as starting ma-terials. The indole compound 3 and the side chain were condensed and process byhydrolysis, replace, reduc-tion and, hydrogenolysis to get the target compound via total six steps. The results showed that： The structure of the target compound was confirmed by ESI-MS and ~1H-NMR. The total yield was 44%, and HPLC purity was more than 99.3%. The improved process conditions are mild, the steps are greatly shortened, the byproducts are greatly reduced, the post-treatment is simple and suitable for industrial production.