posted on 2019-01-23, 12:52authored byFangyu Du, Qifan Zhou, Yajie Shi, Miao Yu, Wenjiao Sun, Guoliang Chen
A practical synthetic route to regorafenib, in which the target compound was obtained via a 10-step synthesis starting from 2-picolinic acid, 4-chloro-3-(trifluoromethyl)aniline, and 3-fluorophenol, is reported. Crucial to the strategy is the preparation of 4-amino-3-fluorophenol via Fries and Beckman rearrangements using an economical and practical protocol. The main advantages of the route include inexpensive starting materials and an acceptable overall yield. A scale-up experiment was carried out to provide regorafenib with 99.96% purity in 46.5% total yield.
Funding
This work was financially supported by the Liaoning Provincial Natural Science Foundation of China [No. 201602707].