A concise synthesis of Fingolimod: an orally available drug for treating multiple sclerosis

Chemistry Central Journal

Lei Yao¹  Lei Bi²  Xinfa Bai¹  Kai Chen¹  Ning Yan¹ 

[1]School of Pharmacy, Yantai University, Yantai 264005, Shandong, China

[2]School of Chemistry and Chemical Engineering, Anhui University of Technology, Maanshan 243002, Anhui, China

关键词: Immunosuppressant;    3-nitropropionic acid;    Fingolimod;   

Others  :  1213784
DOI  :  10.1186/s13065-015-0081-8

 received in 2014-08-29, accepted in 2015-01-13,  发布年份 2015

【 摘 要 】

A concise route for the synthesis of Fingolimod is reported. Starting from n-octylbenzene and 3-nitropropionic acid, a sequence of reactions consisting of Friedel-Crafts acylation, reduction, and double Henry reaction, followed by hydrogenation were applied to prepare Fingolimod with a yield of 31%, and an overall atom economy of 82.7%.

【 授权许可】

   
2015 Yan et al.; licensee Springer.

【 图 表 】

Figure 1.

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• [16]Compound 4 has been reported in the following patents: WO2012146980; WO2012056458; CN1765872.
• [17]In patent WO2012/146980, the compound 6 was obtained by a similar sequence: Friedel-Crafts reaction of n-octylbenzene and 3-chloropropanyl chloride, then displacement of Cl with nitro group, followed a reduction of carbonyl by triethylsilane and TiCl4.
• [18]3-nitropropionic acid is toxic especially to the central nervous system. Fortunately, it is solid and easily to handle. The operator was strongly recommended to ware glove and mask.