3,5-Dichlorobenzaldehyde → N-(3,5-Dichlorobenzyl)-1-(4-fluorophenyl)methanamine

Participants

Reaction Steps

To a solution of 3,5-dichlorobenzaldehyde (3.9 g, 22.3 mmol) in 2-propanol (20 mL) and CH2Cl2 (20 mL) was added 4-fluorobenzylamine (2.93 mL, 25.6 mmol). The resulting mixture was stirred at rt for 1 h. The mixture was cooled to ice bath temperature and was treated with sodium triacetoxyborohydride (7.56 g, 35.7 mmol) under N2 atmosphere. The resulting mixture was stirred at rt for 22 h. To the reaction mixture was added saturated aq NaHCO3 solution and it was stirred for 0.2 h, and concentrated in vacuo. The residue was mixed 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 silica gel column chromatography on silica gel to obtain (ISCO. Condition: 40 g column. Eluents: 0-6% of B, gradient, solvent A: CH2Cl2, solvent B: ethyl acetate (5% 2 M ammonia in MeOH). 35 min run. The desired product peak came from 5 min to 15 min) the desired product as a colorless oil (5.6 g, 80%). 1H NMR (CDCl3): δ 7.34-7.27 (m, 5H), 7.08-7.03 (m, 2H), 3.78 (s, 2H), 3.77 (s, 2H), 1.85 (bs, 1H); MS (ESI): [M+H]+=284.0.

Provenance & Evidence