Boron tribromide → N,N-diethyl-4-[3-hydroxybenzyl(1-propylpiperidin-4-yl)amino]benzamide

Participants

Reaction Steps

A solution of N,N-diethyl-4-[3-methoxybenzyl(1-propylpiperidin-4-yl)amino]benzamide (Compound 1) in 20 mL of dry dichloromethane was cooled to −78° C. under Argon. A solution of boron tribromide (6.44 mL, 6.44 mmol, 1.0 M) in dichloromethane was added dropwise. The reaction mixture was allowed to warm to ambient temperature overnight. After 21 h of stirring, the reaction mixture was poured into saturated aqueous sodium bicarbonate solution (30 mL). The layers were separated, and the aqueous solution was extracted twice (30 mL) with dichloromethane. The organic extracts were combined and dried (Na2SO4). Evaporation of the solvent afforded a yellow-brown glass. This material was suspended in 50 mL of saturated aqueous sodium carbonate solution and refluxed 20 h. After cooling, the reaction mixture was poured into a separatory funnel and extracted three times with chloroform. The organic extracts were combined and dried (Na2SO4). Evaporation of the solvent afforded a brown foam. This material was purified by preparative thin layer chromatography on two 20 cm×20 cm tapered silica gel plates with 3% methanol-chloroform. After three solvent runs, 0.04 g (9%) of N,N-diethyl-4-[3-hydroxybenzyl(1-propylpiperidin-4-yl)amino]benzamide was obtained as a yellow solid. MS (ES), m/z 424 (MH+). 300 MHz 1H NMR (CDCl3) δ0.89 (t, J=7.3 Hz, 3H), 1.18 (t, J=7.0 Hz, 6H), 1.43-1.61 (m, 2H), 1.67-1.88 (m, 4H), 1.95-2.14 (m, 2H), 2.28-2.39 (m, 2H), 3.01 (br d, J=11.3 Hz, 2H), 3.26-3.54 (br m, 2H), 3.69-3.86 (br m, 1H), 4.37 (br s, 2H), 6.52-6.66 (m, 4H), 6.70 (d, J=7.6 Hz, 1H), 7.12 (t, J=7.7 Hz, 1H), 7.16-7.29 (m, 2H).

Provenance & Evidence