Читать книгу Routes to Essential Medicines - Peter J. Harrington - Страница 75

Antineoplastics and Immunosuppressives/Hormones and Antihormones

A β‐hydroxythioether is often formed by ring opening of an epoxide by a thiol.

Discussion. Bicalutamide is a 1 : 1 mixture of (R)‐ and (S)‐enantiomers. The sulfone is formed in the final step by oxidation of the thioether. The thioether is formed by ring opening of the epoxide by 4‐fluorothiophenol.

The epoxide is formed by epoxidation of the acrylamide. The acrylamide is formed by reaction of methacryloyl chloride with the amine. Methacryloyl chloride is formed from methacrylic acid. The amine, 4‐amino‐2‐(trifluoromethyl)benzonitrile, is formed by reaction of 4‐chloro‐3‐(trifluoromethyl)aniline with cuprous cyanide. 4‐Chloro‐3‐(trifluoromethyl)aniline is formed by chlorination of 3‐(trifluoromethyl)aniline. (How selective is the chlorination? What conditions are associated with the highest selectivity for formation of 4‐chloro‐3‐(trifluoromethyl)aniline?)

4‐Fluorothiophenol is formed by reduction of the disulfide. The disulfide is formed by reduction of the sulfinate salt. The sulfinate salt is formed by reduction of 4‐fluorobenzenesulfonyl chloride.