Research and development of a second-generation process for oseltmivir phosphate, prodrug for a neuraminidase inhibitor

被引:94
作者
Harrington, PJ [1 ]
Brown, JD [1 ]
Foderaro, T [1 ]
Hughes, RC [1 ]
机构
[1] Roche Colorado Corp, Boulder Technol Ctr, Boulder, CO 80301 USA
关键词
D O I
10.1021/op0302107
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
A second-generation manufacturing process from a shikimic acid-derived epoxide to oseltamivir phosphate features a magnesium chloride-amine complex-catalyzed ring opening of the epoxide by tert-butylamine, a selective O-sulfonylation of the resulting tert-butylamino alcohol, a surprisingly efficient cleavage of a tert-butyl group from an aliphatic tert-butylamide, and the isolation of oseltamivir phosphate from a palladium-catalyzed allyl transfer reaction mixture. The overall yield from the epoxide to oseltamivir phosphate has been increased from 27 to 29% or 35-38% for two previous processes, respectively, to 61%.
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页码:86 / 91
页数:6
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