Dimethyl Sulfoxide → 4-(4-Chlorophenyl)-1-(imidazol-1-yl)butan-2-one

Participants

Reaction Steps

To a mixture of 1-(4-(4-chlorophenyl)-2-hydroxybutyl)-imidazole (9.0 kg, 35.9 mol) and trimethylamine-sulfur trioxide complex, 2.25 equivalents (11.25 kg, 80.9 mol), was added triethylamine (45 L, 32.7 kg, 323 mol), dimethyl sulfoxide (40.5 L, 44.5 kg, 570 mol), and methylene chloride (18 L). The resulting mixture was heated to 36°-38° C. and stirred for a minimum of 16 hours. Reaction completion was monitored by thin layer chromatography (10% methanol/methylene chloride+2% NH4OH). Upon completion of reaction, the reaction mixture was cooled to 20°-22° C. The temperature was maintained below 27° C. while 40.5 liters of water were added over a period of 15 to 30 minutes. Hexane (54 L) was then slowly added over a period of 15 to 30 minutes at 20°-25° C. Water (81 L) was then added to the mixture over a period of 30-60 minutes while the temperature was maintained at 20°-25° C. The resulting mixture was allowed to stand at 20°-22° C. for 1 to 2 hours. The mixture was filtered and the filter cake washed twice with water and then twice with hexane and dried under vacuum at 48°-51° C. to afford 4-(4-chlorophenyl)-1-(imidazol-1-yl)butan-2-one, 8.30 kg (93% yield).

Provenance & Evidence