Methanol → (2-Bromo-5-fluorophenyl)methanamine

To a solution of 2-bromo-5-fluorobenzonitrile (3.0 g, 15.00 mmol) and NaBH4 (1.419 g, 37.5 mmol) in THF (30 mL) was slowly added TFA (3.47 mL, 45.0 mmol) over a period of 20 min. The resulting mixture was stirred at rt for 16 hours, then MeOH (10 mL) was added and the mixture was stirred for another 30 min. It was then diluted with EtOAc (200 mL), washed with water, dried over Na2SO4 and evaporated. The residue was purified on an 80 g Thompson silica cartridge (3% to 100% B in Hexanes, 1200 mL, B: 10% MeOH in EtOAc). The desired product was obtained as a colorless oil (1.70 g, 8.33 mmol, 55.5% yield). LC/MS (0.647 min, MH+: 205.92). 1H NMR (500 MHz, DMSO-d6) δ ppm 7.59 (1H, dd, J=8.85, 5.49 Hz), 7.43 (1H, dd, J=10.07, 3.05 Hz), 7.05 (1H, td, J=8.47, 3.20 Hz), 3.72 (3H, s), 2.00 (2H, br. s.).

1. customof 20 min
2. stirringthe mixture was stirred for another 30 min
3. washwashed with water
4. dry with materialdried over Na2SO4
5. customevaporated
6. customThe residue was purified on an 80 g Thompson silica cartridge (3% to 100% B in Hexanes, 1200 mL, B: 10% MeOH in EtOAc)

ORD record

ord-a91db8c9524645b4a51de72ff4cc1c0d

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08309577B2