有机化学 ›› 2017, Vol. 37 ›› Issue (9): 2430-2434.DOI: 10.6023/cjoc201704009 上一篇    下一篇

研究简报

利用过二硫酸盐氧化消除2-碘双氢非那雄胺制备非那雄胺

毛冀川a, 申玉良b, 曹春雨b, 舒志坚b, 郑良彬b, 许新华a   

  1. a 湖南大学化工学院 长沙 410082;
    b 湖南玉新药业有限公司 邵阳 422000
  • 收稿日期:2017-04-08 修回日期:2017-05-09 出版日期:2017-09-25 发布日期:2017-05-17
  • 通讯作者: 许新华 E-mail:xhx1581@hnu.edu.cn
  • 基金资助:

    湖南省科技重大专项(No.2014FJ1010)资助项目.

Preparation of Finasteride via Oxidative Elimination of 2-Iododihydrofinasteride by Using Peroxydisulfates as Oxidizing Agents

Mao Jichuana, Shen Yuliangb, Cao Chunyub, Shu Zhijianb, Zheng Liangbinb, Xu Xinhuaa   

  1. a College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082;
    b Limited Liability Company of Yu Xin Phamacy, Shaoyang 422000
  • Received:2017-04-08 Revised:2017-05-09 Online:2017-09-25 Published:2017-05-17
  • Contact: 10.6023/cjoc201704009 E-mail:xhx1581@hnu.edu.cn
  • Supported by:

    Project supported by the Important Science & Technology Specific Projects in Hunan Province (No. 2014FJ1010).

系统考察了不同碱及氧化剂对2-碘二双氢非那雄胺(2a)氧化消除反应的影响,实验结果表明,当以K2S2O8为氧化剂时,反应效果最佳.以K2S2O8为氧化剂,探索了溶剂、K2S2O8用量、温度、时间对反应的影响,获得最佳反应条件为:四氢呋喃(THF)为溶剂,室温反应10 h,K2S2O8与2-碘二双氢非那雄胺(2a)的投料比为2:1.在该最优化条件下,非那雄胺(3a)收率为96%,纯度为99.6%.同时,该条件也适用于2-碘-3-氧代-4-氮杂-5α-雄甾-17β-甲酸(2b)和2-碘-3-氧代-4-氮杂-5α-雄甾-17β-甲酸甲酯(2c)的氧化消除反应,得到相应目标产物收率和纯度均高.本方法具有反应条件温和、产品收率和纯度均高且对环境友好等优点.

关键词: 非那雄胺, 过二硫酸盐, 氧化消除, 2-碘双氢非那雄胺

The influence of various bases and oxidizing agents to the oxidation elimination of 2-iododihydrofinasteride (2a) was explored, and the results showed that K2S2O8 is the best oxidizing agent. The influences of solvents, amount of K2S2O8, temperature and reaction time on the oxidation elimination were also investigated, and the optimal conditions were obtained as follow:tetrahydrofuran (THF), 10 h, room temperature, nK2S2O8:n2a=2:1. Finasteride 3a was obtained in the yield of 96.3% with the purity of 99.6%, when the reaction was performed under optimal conditions. The optimal conditions are also suitable for the oxidation elimination of 2-iodo-3-oxo-4-aza-5α-androstane-17β-carboxylic acid (2b) and 2-iodo-3-oxo-4-aza-5α-androstane-17β-carboxylate (2c), for giving the desired products in good yield and high purity. Other advantages include mild conditions, excellent yields, high purity and friendly to environment.

Key words: finasteride, peroxydisulfate, oxidation elimination, 2-iododihydrofinasteride