Tetrahydrofuran → HCID 178489084, compound

Participants

Reaction Conditions

Reaction Steps

To a cooled (-78° C.) solution of 1-(1-ethoxy-ethyl)-4-(fluorophenyl)-5-(4-methoxyphenyl)-1H-imidazole (5.0 g, 14.8 mmoles) and tetramethylethylenediamine (2.60 ml, 17.0 mmoles) in 75 ml of tetrahydrofuran was added 12.1 ml of 2.1M n-butyl lithium dropwise. The mixture was stirred for 15 minutes at -78° C., and then N-(trimethylsilyl)hexafluoroacetone imine (5.84 g, 24.6 mmoles) was added dropwise. After stirring for an additional hour at -78° C., the mixture was warmed to 0° C. Then, 55 ml of saturated sodium bicarbonate was added dropwise and the reaction mixture was brought to room temperature. The organic layer was separated and the solvent removed in vacuo. The residue was stirred overnight with a mixture of 110 ml of ethanol and 55 ml of 2N hydrochloric acid. The ethanol was removed under vacuum. The aqueous residue was extracted thoroughly with ether, dried over anhydrous magnesium sulfate and concentrated to dryness to afford 5.42 g (84%) of crude product. The residual oil was chromatographed on silica gel eluting with ether/hexane (1:4). The product fractions were recrystallized from butyl chloride/hexane to give 3.3 g (51.5%) of the title compound as white crystals, m.p. 123°-124° C.

Provenance & Evidence