p-Toluenesulfonic acid monohydrate → 2-(4-fluorophenyl)-1-(4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole

Participants

Reaction Steps

A mixture of 2-(4-fluorophenyl)-4-hydroxy-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-4,5-dihydro-1H-imidazole (Step 2) (2.8 g, 7 mmol) and p-toluenesulfonic acid monohydrate (300 mg) in toluene (200 mL) was heated to reflux for 72 hours. The reaction mixture was cooled and the solvent removed under reduced pressure. The crude residue was redissolved in methylene chloride and washed with water, aqueous sodium bicarbonate and brine. After drying (Na2SO4), filtration and concentration in vacuo, the crude mixture (3.2 g) was purified by chromatography on silica gel using toluene/ethyl acetate (1/1) to give pure 2-(4-fluorophenyl)-1-(4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole (1.38 g, 52%) as a white solid: mp (DSC) 205.5° C. Anal. Calc'd for C17H12N2F4SO2: C, 53.13; H, 3.15; N, 7.29; S, 8.34. Found: C, 53.18; H. 3.17; N, 7.26; S, 8.57.

Provenance & Evidence