1005291-43-9

41404-58-4

68-12-2

1005291-43-9

Slowly add n-butyllithium (2.4 M in THF, 55.5 mL) dropwise to a solution of diisopropylamine (24.64 g) in THF (100 mL) at -70 °C. During the dropwise addition, ensure that the temperature of the reaction system does not exceed -70 °C. After the dropwise addition was completed, the temperature was slowly warmed to -10 °C and subsequently cooled to -70 °C again. At -70 °C, a solution of 2-bromo-5-fluoropyridine (19.48 g) in THF (100 mL) was added to the reaction system, kept at -70 °C and stirred for 2 hours. Subsequently, N,N-dimethylformamide (16.3 g) was added slowly and dropwise, maintaining the temperature at -70 °C and continuing to stir for 2 hours. 4M hydrochloric acid-dioxane solution (111 mL) was added slowly, ensuring that the temperature of the reaction system did not exceed -70 °C during the dropwise addition. Upon completion of the reaction, the reaction mixture was diluted with ethyl acetate and washed sequentially with water and saturated brine solution. The organic phase was separated, dried with anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure. Finally, the residue was purified by silica gel column chromatography to afford the target product 2-bromo-5-fluoro-4-pyridinecarboxaldehyde (20.28 g).