22918-01-0

68-12-2

1289197-78-9

GENERAL STEPS: To an anhydrous tetrahydrofuran (40 mL) solution of 2-bromo-4-chloropyridine (1.6 g, 8.0 mmol) was slowly added lithium diisopropylammonium solution (5.0 mL, 10.0 mmol, 2.0 M) over 5 minutes at -70 °C and stirring was continued for 1 hour at -70 °C. Subsequently, anhydrous N,N-dimethylformamide (1.3 g) was added dropwise over 3 minutes and the reaction mixture was stirred at the same temperature for another 30 minutes. After completion of the reaction, the reaction was quenched with saturated ammonium chloride solution (30 mL) and extracted with ethyl acetate (20 mL x 3). The organic layers were combined, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using petroleum ether/ethyl acetate (20:1) as eluent to afford 2-bromo-4-chloropyridine-3-carboxaldehyde (114a) as a yellow solid (900 mg, 48% yield).1H NMR (500 MHz, DMSO) δ 10.21 (s, 1H), 8.52 (d, J = 5.5 Hz, 1H), 7.79 (d, J = 5.0 Hz, 1H).