4-Fluorobenzaldehyde → N-(3,5-Dichlorobenzyl)-N-(4-fluorobenzyl)-3-((4-fluorobenzylamino)methyl)benzamide

Participants

Reaction Steps

To a solution of 3-(aminomethyl)-N-(3,5-dichlorobenzyl)-N-(4-fluorobenzyl)benzamide (0.6 g, 1.44 mmol) in CH2Cl2 (6.0 mL) and 2-propanol (6.0 mL) was added 4-fluorobenzaldehyde (0.16 mL, 1.44 mmol). The resulting mixture was stirred at rt for 1.5 h. The reaction mixture was cooled to ice bath temperature and was added sodium triacetoxyborohydride (0.49 g, 2.30 mmol) under N2 atmosphere. The resulting mixture was stirred at rt for 20 h. To the reaction mixture was added saturated aq NaHCO3 solution and the mixture was stirred for 20 minutes. The mixture was concentrated, and the residue was diluted with ethyl acetate and saturated aq NaHCO3 solution. The organic layer was separated, washed with brine, dried over MgSO4 and concentrated. The residue was purified by flash chromatography on silica gel (ISCO. condition: 24 g column; eluents: 0-25% of ethyl acetate in CH2Cl2, gradient over 40 minutes) to obtain the desired product as colorless oil (0.47, 63%). 1H NMR (CDCl3): δ 7.55-7.29 (m, 7H), 7.17-7.00 (m, 8H), 4.70-4.63 (m, 2H), 4.43-4.36 (m, 2H), 3.82 (s, 2H), 3.77 (s, 2H); MS (ESI): [M+H]+=524.9.

Provenance & Evidence