N-[4-Cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)thio]-2-hydroxy-2-methylpropionamide

Chemical Properties

White Solid

Uses

Bicalutamide intermediate.

Synthesis

Example 1 Preparation of N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)thio]-2-hydroxy-2-methylpropanamide: 4-Fluorobenzenethiol (21 g) was dissolved in methanol (65 ml) and cooled to 0°C. 50% aqueous sodium hydroxide solution (14g) was added in batches under stirring. The reaction mixture was stirred at 0°C for 30 min, followed by continued stirring at 25°C for 1 hr. N-[4-cyano-3-(trifluoromethyl)phenyl]-2-methyl oxirane amide (40 g) was added to the reaction system and the reaction was stirred at room temperature for 2 hours. The progress of the reaction was monitored by thin layer chromatography (TLC). After completion of the reaction, water (100 ml) was added to the mixture and the pH was adjusted to below 7 with concentrated hydrochloric acid. Methanol was removed by distillation under reduced pressure until no methanol was distilled. The resulting suspension was stirred at 5°C for 3 h. The solid product was collected by filtration and washed with water (2 x 40 ml). Finally, the solid was dried under vacuum at 50-60°C to afford the target product N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)thio]-2-hydroxy-2-methylpropanamide 58 g in 98% yield.

References

[1] Patent: US2007/27211, 2007, A1. Location in patent: Page/Page column 2; 4
[2] Patent: US2003/191337, 2003, A1. Location in patent: Page/Page column 5; 11
[3] Patent: US2013/274501, 2013, A1. Location in patent: Paragraph 0107; 0108; 0109
[4] Patent: US2003/191337, 2003, A1. Location in patent: Page/Page column 12; 13