Acetic Acid → 4-(4-Acetamido-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-N-[3,5-bis(trifluoromethyl)benzyl]butylamine

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-(4-acetamido-4-phenylpiperidino)-2-(3,4-dichlorophenyl)butylamine (0.30 g) in methanol (3 mL) was added 3,5-bis(trifluoromethyl)benzaldehyde (0.088 mL) and the mixture cooled to 0° C. To this stirred mixture was sequentially added acetic acid (0.046 mL) and a solution of sodium cyanoborohydride (0.50 g) in methanol (1 mL). The mixture was allowed to slowly warm to room temperature overnight and was diluted with dichloromethane (5 mL), water (5 mL), and hydrochloric acid (1N, 5 mL). The layers were separated, and the aqueous layer was extracted three times with dichloromethane (10 mL). The acidic aqueous layer was made basic with aqueous sodium hydroxide (1N, 5 mL) and then extracted with 5:1 dichloromethane:methanol (3×10 mL). The combined organic layers were washed (brine), dried, filtered and evaporated to afford an oil which was purified by chromatography, with dichloromethane:methanol (40:1) as eluent. Evaporation of the appropriate fractions afforded a partial hydrate of the title compound as a white solid (0.154 g); mp 66°-68° C.; NMR: 7.82 (s,3), 7.75 (s,1), 7.50 (m,2), 7.35-5.15 (m,6), 2.75 (m,1), 2.65-2.55 (m,2), 2.32-1.95 (m,6), 1.85 (s,3), 1.95-1.55 (m,6); MS: m/z=660(M+1, 100%); Rf =0.51 (10:1, dichloromethane:methanol). Analysis for C32H33Cl2F6N3O.0.25 H2O: Calculated: C, 57.79; H, 5.08; N, 6.32; Found: C, 57.68; H, 5.07; N, 6.30.

Provenance & Evidence