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

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.

1. temperatureThe mixture was cooled to ice bath temperature
2. stirringThe resulting mixture was stirred at rt for 22 h
3. stirringwas stirred for 0.2 h
4. concentrationconcentrated in vacuo
5. additionThe residue was mixed with ethyl acetate and saturated aq NaHCO3 solution
6. customThe organic layer was separated
7. washwashed with brine
8. dry with materialdried over MgSO4
9. concentrationconcentrated
10. customThe residue was purified by flash silica gel column chromatography on silica gel
11. customto obtain (ISCO
12. custom35 min

ORD record

ord-7dce9c0a5aad4c2aa2da5ceb55d2613d

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501992B2