Methanol → (4-Bromo-2-chloro-5-fluorophenyl)methanol

Temperature

0 °C

To a solution of methyl 4-bromo-2-chloro-5-fluorobenzoate (18.00 g, 67.28 mmol) in tetrahydrofuran (100 mL) was added methanol (3.0 mL, 74.15 mmol), followed by the addition of lithium borohydride solution (4.0 M in tetrahydrofuran, 33.7 mL, 134.80 mmol) at 0° C. over 30 min. The reaction mixture was stirred for further 10 min at 0° C., and then at ambient temperature for 20 h; 5% sodium hydroxide solution (100 mL) was added to the reaction mixture slowly at 0° C. After stirring for 30 min. the reaction mixture was extracted with ethyl acetate (200 mL×3). The organic layer was washed with brine, and concentrated in vacuo to afford the title compound as a pale yellow solid (16.00 g, 99%): 1H NMR (300 MHz, CDCl3) δ 7.51 (d, J=6.0 Hz, 1H), 7.30 (d, J=9.0 Hz, 1H), 4.69 (s, 2H), 2.08 (s, 1H).

1. waitat ambient temperature for 20 h
2. stirringAfter stirring for 30 min. the reaction mixture
3. extractionwas extracted with ethyl acetate (200 mL×3)
4. washThe organic layer was washed with brine
5. concentrationconcentrated in vacuo

ORD record

ord-b3aca78077074ba2bdbb2e520e0cd9dc

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952169B2