An improved and practical route for the synthesis of enzalutamide and potential impurities study

Abstract An improved and practical synthesis of enzalutamide was accomplished in five steps. Starting from 4-bromo-2-fluoro-benzonic acid, a methyl esterification, Ullmann ligation, methyl esterification, ring closing reaction and final methyl amidation provided the target in 35% total yield with 99.8% purity. Five identified impurities were also synthesized. This efficient and economical procedure avoids the use of highly toxic reagents and multiple recrystallization operations, which is suitable for further industrialization.