Methyl formate → 3,5-Difluoropyridine-4-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

At 0° C. A solution of LDA 2M in THF (47.792 mL, 95.58 mmol) was diluted with 50 mL THF. It was cooled down to −78° C., then a solution of 3,5-Difluoropyridine (7.886 mL, 86.89 mmol) in 100 mL THF was added dropwise while maintaining the temperature below −70° C., (complete addition in 20 min). It gave a yellow suspension. The reaction mixture was stirred 3 h at −78° C. A solution of Methyl formate (10.8 mL, 173.79 mmol) in 25 mL THF was added dropwise in 15 min. The reaction mixture became a pale yellow solution. It was stirred 45 min at −75° C. and then transferred via cannula to a stirred solution of 100 mL sat aq NaHCO3 held at about 0° C. It was extracted twice with EtOAc and the combined organic phases were washed with brine and dried with Na2SO4. The solvent was evaporated (165 mbar, 30° C.), 36.7 g of residue were obtained as a yellow liquid. The crude product was purified by flash chromatography (Solvent: CH2Cl2). The product was isolated as a pale yellow oil (7.85 g), which crystallized upon standing.

Provenance & Evidence