Hydrochloric Acid → HCID 9908569, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of oxalyl chloride (0.51 ml, 0.74 g, 5.8 mmol) in dichloromethane (13 ml) at -78° C. under argon was added dimethylsulfoxide (0.91 g, 12 mmol) in dichloromethane (2.5 ml) at such a rate as to keep the temperature below -50° C. After stirring 20 minutes at -78° C., α-[1-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]-4-piperidinyl]-lH-benzimidazole-2-methanol (2.3 g, 5.2 mmol) was added in dichloromethane (20 ml), dropwise, via syringe. After an additional 20 minutes of stirring at -78° C., triethylamine (3.0 ml, 22 mmol) was added, the cooling bath was removed, and the solution was allowed to stir for 1 hour. Water was added, the layers separated, and the aqueous layer extracted with dichloromethane. The combined organic layers were dried (MgSO4), and filtered through a pad of silica (eluting with acetone). The eluent was concentrated to give a white foam. The foam was dissolved in methanol (50 ml), treated with 10% hydrochloric acid, and stirred for 3 hours. The solution was neutralized with 5% sodium bicarbonate, concentrated, and extracted twice with dichloromethane. The combined organic layers were dried (MgSO4), concentrated, and the resulting solid recrystallized from ethyl acetate to afford 4-[4-(lH-benzimidazol-2-yl-carbonyl)-1-piperidinyl]-1-(4-fluorophenyl)-1-butanone as an off-white solid m.p. 155-156° C.

Provenance & Evidence