Ethanol → HCID 54074511, compound

Participants

Reaction Steps

Using the general procedure of S. Ohara, K. Kawasaki, Y. Kawamura, and M. Tanaka (J. Heterocyclic Chem., 1990, 27, 487-495), silica gel (EM silica gel 60, 230-400 mesh) was dried under vacuum at 180° C. for 2 h. A suspension of 1.80 g of this activated silica gel was stirred in 9 mL of dry toluene and 3-(3-bromo-4-methoxyphenyl)-3-(dimethylhydrazono)-1,1,1-trifluoropropan-2-one (250 mg 0.71 mmol) was added as a solution in 5 mL of toluene. The resulting suspension was heated to reflux for 48 h, then allowed to cool to room temperature and stirred overnight. After the addition of 95% ethanol (20 mL) the mixture was stirred for 10 min and filtered. The silica gel was stirred with 20 mL of 95% ethanol and filtered, and the process was repeated again. Evaporation of the combined filtrates gave a pale amber oil. Flash column chromatography on 15 g of silica gel eluting with 10% ethyl acetate in hexane followed by 15% ethyl acetate in hexane gave 167 mg of 4-(3-bromo-4-methoxyphenyl)-5-trifluoromethyl-1-methylimidazole and 5-(3-bromo-4-methoxyphenyl)-4-trifluoromethyl-1-methylimidazole as a 6:1 mixture as determined by NMR. This material was recrystallized from a 65° C. solution in hexane (0.75 mL) and toluene (0.15 mL) cooled to -10° C. Recrystallization again from a 65° C. solution in hexane (0.75 mL) and toluene (0.15 mL) cooled to room temperature gave 112 mg of 4-(3-bromo-4-methoxyphenyl)-5-trifluoromethyl-1-methylimidazole as white crystals. Concentration of the mother liquors yielded 48 mg of 4-(3-bromo-4-methoxyphenyl)-5-trifluoromethyl-1-methylimidazole and 5-(3-bromo-4-methoxyphenyl)-4-trifluoromethyl-1-methylimidazole as a 1:1 mixture as determined by NMR. 4-(3-Bromo-4-methoxyphenyl)-5-trifluoromethyl-1-methylimidazole: 1H NMR (400 MHz, CDCl3): δ 7.78 (d, 1H, J=2 Hz), 7.75 (s, 1H), 7.47 (bd, 1H, J=8 Hz), 6.93 (d, 1H, J=8 Hz), 3.94 (s, 3H), 3.81 (s, 3H). Mass spectrum (ESI): m/e=335 (M+1).

Provenance & Evidence