1-Bromo-3,3,3-trifluoroacetone

• Thiobenzamide [T0194]
• 1-Bromo-3,3,3-trifluoroacetone [B1240]
• p-Toluenesulfonic Acid Monohydrate (= TsOH·H₂O) [T0267]
• Ethanol
• Toluene

1-Bromo-3,3,3-trifluoroacetone (0.252 mL, 2.4 mmol, 1.2 eq.) was added to a ethanol (20 mL) solution of thiobenzamide (274 mg, 2.0 mmol) at room temperature and the mixture was refluxed for 4 hours. Then the solvent was removed under reduced pressure. Toluene (20 mL) and TsOH·H₂O (190 mg, 1.0 mmol, 0.5 eq.) were added to the residue and refluxed for overnight. After that the solvent was removed under reduced pressure and the residue was purified by column chromatography (on silica gel, ethyl acetate:hexane = 0:1 - 1:10) to give 2-phenyl-4-(trifluoromethyl)thiazole as a pale yellow solid (387 mg, 84% yield).

The reaction mixture was monitored by UPLC.

2-Phenyl-4-(trifluoromethyl)thiazole (1)

¹H NMR (400 MHz, CDCl₃); δ 7.99-7.97 (m, 2H), 7.74 (s, 1H), 7.49-7.46 (m, 3H).

• Optimization of Novel 1-Methyl-1H-Pyrazole-5-carboxamides Leads to High Potency Larval Development Inhibitors of the Barber’s Pole Worm
• T. G. Le, A. Kundu, A. Ghoshal, N. H. Nguyen, S. Preston, Y. Jiao, B. Ruan, L. Xue, F. Huang, J. Keiser, A. Hofmann, B. C. H. Chang, J. Garcia-Bustos, A. Jabbar, T. N. C. Wells, M. J. Palmer, R. B. Gasser, J. B. Baell, J. Med. Chem. 2018, 61, 10875.