Dimethylformamide → 4-Bromo-2,5-difluorobenzaldehyde

Temperature

-78 °C

To a solution of 2,5-dibromo-1,4-difluorobenzene (10.0 g, 36.77 mmol) in diethyl ether (150 mL) at −78° C. was added n-butyl lithium (2.5 M in Hexanes, 14.86 mL, 37.15 mmol) dropwise under nitrogen. The reaction mixture was stirred at −78° C. for 30 min. Dry DMF (3.13 mL, 40.46 mmol) in diethyl ether (10 mL) was added dropwise and reaction was slowly warmed to room temperature over 2 h. The reaction was quenched with aqueous saturated ammonium chloride solution (25 mL) and extracted with diethyl ether. The organic phase was washed with saturated brine solution, dried (Na2SO4), filtered, and concentrated under reduced pressure (Note: Product is highly volatile). The crude product was purified by flash chromatography (SiO2, eluting with 2-20% ethyl acetate in hexanes) to provide the title compound as a pale yellow solid (7.0 g, 86%): 1H NMR (400 MHz, CDCl3): δ 7.50 (dd, J=5.08, 8.92 Hz, 1H), 7.62 (dd, J=5.80, 7.68 Hz, 1H), 10.30 (d, J=2.76 Hz, 1H).

1. customreaction
2. temperaturewas slowly warmed to room temperature over 2 h
3. customThe reaction was quenched with aqueous saturated ammonium chloride solution (25 mL)
4. extractionextracted with diethyl ether
5. washThe organic phase was washed with saturated brine solution
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure (
9. customThe crude product was purified by flash chromatography (SiO2, eluting with 2-20% ethyl acetate in hexanes)

ORD record

ord-afdf9c10bed24658ac63f0682cfb338e

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09113629B2