Dimethylformamide → 4-Chloro-2-(fluoromethyl)benzaldehyde

Temperature

-75 °C

To a solution of 1-bromo-4-chloro-2-(fluoromethyl)benzene (0.5 g, 2.2 mmol) in anhydrous THF (20 mL) was added a solution of n-butyl lithium (1.0 mL, 2.5 M in hexanes, 2.5 mmol) in anhydrous THF (10 mL), at about −75° C. The resulting mixture was stirred for about 30 min at about −75° C. and then DMF (0.34 mL, 4.5 mmol) was added slowly. Over about 1 h the mixture was warmed to about −55° C. and then saturated aqueous ammonium chloride (10 mL) was added followed by diethyl ether (50 mL). The layers were separated and the organic layer was washed with brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, diethyl ether/hexanes 1:3) to give 4-chloro-2-(fluoromethyl)benzaldehyde (0.15 g, 0.87 mmol, 39%) as a white solid: 1H-NMR (CDCl3, Bruker 400 MHz) δ 5.85 (2 H, d, J=47.8 Hz) 7.52 (1 H, dd, J=8.2, 2.0 Hz) 7.72 (1 H, br s) 7.80 (1 H, dd, J=8.2, 1.4 Hz) 10.04 (1 H, d, J=1.4 Hz).

1. customat about −75° C
2. temperatureOver about 1 h the mixture was warmed to about −55° C.
3. customThe layers were separated
4. washthe organic layer was washed with brine (20 mL)
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by column chromatography (SiO2, diethyl ether/hexanes 1:3)

ORD record

ord-f01793e8037a4104b98b53ae9cec54af

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09150592B2