Dimethylformamide → 6-Bromo-2-fluoro-3-methoxybenzaldehyde

Participants

Reaction Conditions

Reaction Steps

To a solution of diisopropylamine (11 mL) in anhydrous THF (50 mL) was cooled to 0° C. and was added 1.6 M n-butyl lithium/hexanes (47 mL) dropwise under nitrogen atmosphere. The mixture was stirred for 10 min at 0° C. and was then cooled to −78° C. with an acetone dry ice bath. A solution of 4-bromo-2-fluoro-1-methoxybenzene (7.9 mL, 61 mmol) in anhydrous THF (50 mL) was added dropwise. The mixture was then allowed to stir for 30 min at −78° C. DMF (7.5 mL) was added dropwise at −78° C. The reaction was stirred for 1 h at room temperature. Half of the solvent from the solution was removed under reduced pressure and the solution was extracted using ethyl acetate, water (300 mL), and 1 M HCl (65 mL). The organic layer was washed with brine, dried over anhydrous sodium sulfate, and filtered. The solvent was removed under reduced pressure. The residue was crystallized by washing with hexanes. The solid was collected by filtration and dried under reduced pressure to give 6-bromo-2-fluoro-3-methoxybenzaldehyde (8.21 g, 58%).

Provenance & Evidence