醋酸巴多昔芬的合成工艺改进

醋酸巴多昔芬的合成工艺改进

张春来,姜琦,宣景安,李国贤

扬子江药业集团有限公司,扬子江药业集团有限公司,扬子江药业集团有限公司,扬子江药业集团有限公司

收稿日期:2014-08-04 修回日期:2014-10-20 出版日期:2014-10-25 发布日期:2014-10-25

An improved process for synthesis of bazedoxifene acetate

张春来,姜琦,宣景安 and 李国贤

Yangtze River Pharmaceutical Group Co.,Ltd.,Yangtze River Pharmaceutical Group Co.,Ltd.,Yangtze River Pharmaceutical Group Co.,Ltd.

Received:2014-08-04 Revised:2014-10-20 Online:2014-10-25 Published:2014-10-25

摘要/Abstract

摘要： 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HPLC纯度99.5%以上。结论：改进后的工艺步骤大大缩短,且操作简单,收率和纯度较高,适合工业化生产。

Abstract: 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 substituent and chlorination. The stemnucleus was obtained by condensation taking 4-Benzyloxypropiophenone and 4-Methoxyphenylhydrazine hydrochloride as raw materials; The side chain and the stemnucleus were condensed and process by acidification, hydrogenolysis, neutralization and acidification with acetic acid to get the target compound via total six steps. Result: The structure of the target compound was confirmed by MS and 1H-NMR. The total yield was 53%, and the HPLC purity was more than 99.5%. Conclusion: The improved process with short steps, simple operation, good yield and purity is feasible for industralization.

张春来,姜琦,宣景安,李国贤. 醋酸巴多昔芬的合成工艺改进[J]. .

张春来,姜琦,宣景安 and 李国贤. An improved process for synthesis of bazedoxifene acetate[J]. .