3-Bromo-1,1,1-trifluoro-2-propanone → 4-(4-hydroxy-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1H-imidazol-2-yl]pyridine

Participants

Reaction Steps

To a mixture of the amidine of step 1 (4.75 g, 16 mmol) and sodium bicarbonate (2.86 g, 34.4 mmol) in isopropanol (400 ml), 3-bromo-1,1,1-trifluoroacetone (2.7 ml, 26 mmol) was added. After heating at 75–80° C. for 24 hours, the reaction mixture was cooled and filtered. The residue was washed with methylene chloride and the combined organic fractions were dried over sodium sulfate, filtered and concentrated. The crude product (16.2 g) was purified by chromatography (silica gel, ethyl acetate/isopropanol (95/5)) to give 4-[4-hydroxy-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1H-imidazol-2-yl]pyridine (1.55 g, 23%) as a white solid: mp 219° C., Anal. Calc'd. for C16H14N3SO3F3C, 49.87; H, 3.661; N, 10.90; S, 8.32. Found: C, 49.93; H, 3.51; N, 10.79; S, 8.66.

Provenance & Evidence