Trifluoromethanesulfonic anhydride → Methyl 1-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-4-(3-methylbenzyl)piperidine-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a cold (−78° C.) solution of 3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl alcohol (184 mg, 0.81 mmol) and dilsopropylethylarnine (155 μL, 0.89 mmol) in dichloromethane (3.8 mL), trifluoromethanesulfonic anhydride (143 μL, 0.85 mmol) was added. The resulting mixture was stirred at −78° C. for 20 min., and was treated with a solution of methyl 4-(3-methylbenzyl)piperidine-4-carboxylate hydrochloride salt (276 mg, 0.97 mmol; Example 61, Step B) and diisopropylethylamine (186 μL, 1.07 mmol) in dichloromethane (1 mL). The reaction mixture was stirred at −78° C. for one h., and at room temp. for two h. The resultant solution was concentrated under vacuum, and the residue was partitioned between dichloromethane and aqueous sodium bicarbonate. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The crude product was subjected to high pressure liquid column chromatography on C-18 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid.

Provenance & Evidence