Synthesis
4. To a solution of methyl 6-bromo-3-methoxypyridinecarboxylate (7.56 g) obtained in Step 3 in tetrahydrofuran (THF) (110 mL) was slowly added diisobutylaluminum hydride (DIBAL-H) (1.5 M toluene solution, 24.6 mL) at -78 °C. The reaction mixture was stirred at -78 °C for 1 hour. Subsequently, the reaction mixture was warmed to 0 °C and stirring was continued. Upon completion of the reaction, the reaction was quenched by adding saturated aqueous sodium potassium tartrate (Rochelle salt) to the mixture and extracted with ethyl acetate. The organic layers were combined, washed with saturated sodium chloride (brine) solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent gradient: 0→33% ethyl acetate/hexane) and crystallized from ethyl acetate/hexane mixed solvent to give 6-bromo-3-methoxypyridine-2-carboxaldehyde (5.36 g, 81% yield) as white crystals.
