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

doi:10.6023/cjoc201704009

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

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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

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 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 Jichuan^a, Shen Yuliang^b, Cao Chunyu^b, Shu Zhijian^b, Zheng Liangbin^b, Xu Xinhua^a

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 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).

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1. 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.PDF(789KB)

摘要/Abstract

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:n_2a=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

引用此文

毛冀川, 申玉良, 曹春雨, 舒志坚, 郑良彬, 许新华. 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[J]. 有机化学, 2017, 37(9): 2430-2434.

Mao Jichuan, Shen Yuliang, Cao Chunyu, Shu Zhijian, Zheng Liangbin, Xu Xinhua. Preparation of Finasteride via Oxidative Elimination of 2-Iododihydrofinasteride by Using Peroxydisulfates as Oxidizing Agents[J]. Chin. J. Org. Chem., 2017, 37(9): 2430-2434.

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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

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

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