A solution of 2,6-difluoropyridine (4.95 g, 43.0 mmol) in anhydrous tetrahydrofuran (100 mL) was cooled to -78 °C under nitrogen atmosphere and lithium diisopropylammonium (2.0 M in heptane/tetrahydrofuran/ethylbenzene, 23.0 mL, 46.0 mmol) was added slowly. The reaction mixture was stirred at -78 °C for 30 min before N-formylpiperidine (4.98 g, 44.0 mmol) was added. Stirring was continued at -78 °C for 20 min, followed by the addition of 3 N hydrochloric acid aqueous solution (60 mL) and ether (50 mL). The ether layer was separated and the aqueous layer was extracted with ether (3 x 100 mL). The organic phases were combined and dried over anhydrous sodium sulfate. After filtration, the solvent was removed under reduced pressure and the residue was purified by rapid column chromatography on silica gel (dichloromethane/hexane, 1:1 v/v) to afford 2,6-difluoropyridine-3-carboxaldehyde as a pale yellow liquid (1.41 g, 60% yield).
