Resolution of the nonsteroidal antiandrogen 4'-cyano-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methyl-3'- (trifluoromethyl)-propionanilide and the determination of the absolute configuration of the active enantiomer.

The nonsteroidal antiandrogen 4'-cyano-3-[(4-fluorophenyl)sulfonyl]-2- hydroxy-2-methyl-3'-(trifluoromethyl)-propionanilide (1) (ICI 176334) has been resolved by chromatographic separation of the diastereomeric (R)-camphanyl esters of the precursor thioether 2 followed by hydrolysis and oxidation of the isolated enantiomers. In addition, an asymmetric synthesis of (S)-3-bromo-2-hydroxy-2-methylpropanoic acid (11) and subsequent conversion into the (S)-sulfone 6a has established that the more potent enantiomer of 1 has the R absolute configuration.