General procedure for the synthesis of 5-bromo-2,4-difluorobenzaldehyde from 1,5-dibromo-2,4-difluorobenzene and N,N-dimethylformamide: 1,5-dibromo-2,4-difluorobenzene (17.5 g, 64.2 mmol) was dissolved in ether (100 mL) at -78 °C, and n-butyllithium (2.5 M, 30.8 mL, 77 mmol) was added slowly (2.5 M, 30.8 mL, 77 mmol), over a period of 5 minutes. The reaction mixture was continued to be stirred at -78 °C for 30 min. Subsequently, N,N-dimethylformamide (9.94 mL, 148 mmol) was added all at once and the mixture was stirred at the same temperature for another 30 minutes. After completion of the reaction, the reaction mixture was treated with ethyl acetate and saturated sodium bicarbonate solution. The crude product was purified by silica gel column chromatography using 0-10% ethyl acetate/hexane as eluent to afford the target compound 5-bromo-2,4-difluorobenzaldehyde as a light yellow oil (8.5 g, 60% yield). The product was characterized by 1H NMR (400 MHz, chloroform-d): δ10.26 (s, 1H), 8.14 (t, J=7.5 Hz, 1H), 7.05 (dd, J=9.8,8.0 Hz, 1H).
