4-Bromo-2-fluorobenzaldehyde → 3-(4-Bromo-2-fluorobenzylamino)butan-1-ol

A mixture of 3-aminobutan-1-ol (1.8 g, 20.2 mmol), 4-bromo-2-fluorobenzaldehyde (4.1 g, 20.2 mmol), and ZnCl2 (28 mg, 0.202 mmol) in MeOH (20 mL) was stirred at ambient temperature for 1 hour. To the mixture at 0° C. was added NaBH4 (3.84 g, 101 mmol) and stirred at ambient temperature for 22 hours. The reaction mixture was quenched with H2O and extracted with EtOAc (30 mL×4). The extracts were combined, washed with brine (20 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography using petroleumn ether/EtOAc (5/1) and EtOAc/NEt3 (500/1) as eluting solvents to afford 3-(4-bromo-2-fluorobenzylamino)butan-1-ol as corlorless oil (3.2 g, 57%). 1H-NMR (500 MHz, CDCl3) δ 7.25-7.20 (m, 3H), 3.90 (d, 1H), 3.87-3.83 (m, 1H), 3.77-3.173 (m, 2H), 3.00-2.93 (m, 2H), 1.77-1.71 (m, 1H), 1.59-1.52 (m, 1H), 1.20 (d, 3H); LCMS (ESI): m/z=276.1 [M+H]+.

1. stirringstirred at ambient temperature for 22 hours
2. customThe reaction mixture was quenched with H2O
3. extractionextracted with EtOAc (30 mL×4)
4. washwashed with brine (20 mL)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by silica gel chromatography
9. washas eluting solvents

ORD record

ord-0674202776d445c49de8beb34e006476

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08912219B2