GENERAL STEPS: Lithium (trimethylsilylmethyl) (22 mL, 13.8 wt% hexane solution) was added to a 100 mL three-necked round-bottomed flask and the reaction system cooled to -50 °C. A mixed solution containing 2-fluoropyridine (2.0 g), THF (25 mL), and diisopropylamine (0.13 mL) was slowly added over 1 min while keeping the temperature below -50 °C. After 3 hours of reaction, 1-formylpiperidine (2.4 g) was added over 1 min, also at below -50 °C. Subsequently, the reaction mixture was gradually warmed to room temperature and stirring was continued overnight. Upon completion of the reaction, the reaction was quenched with acetic acid (3 mL) and water (7 mL). The aqueous layer was separated and washed with methyl tert-butyl ether (MTBE, 3 x 25 mL). All organic layers were combined, dried with anhydrous magnesium sulfate (MgSO?) and concentrated under reduced pressure to give 3.79 g of brown oil. Finally, the oily material was purified by silica gel column chromatography, using a hexane solution of 15% ethyl acetate as eluent, to give 2.24 g of 2-fluoro-3-pyridinecarboxaldehyde with a purity of 92.4% (90% yield, corrected for assay).
