Dimethylformamide → 6-Chloro-2-fluoronicotinaldehyde

Participants

Reaction Conditions

Reaction Steps

Diisopropylamine (1.14 ml, 8.0 mmol) was taken up in 8 mL tetrahydrofuran and cooled to −78° C. n-Buyllithium (4.8 ml, 7.6 mmol) was added dropwise. The flask was then warmed to 0° C. in an ice bath and stirred for 30 minutes. The reaction mixture was then added dropwise to a cooled (−78° C.) solution of 2-chloro-6-fluoropyridine (1.0 g, 7.60 mmol) in tetrahydrofuran (25.3 ml). The reaction mixture was stirred at −78° C. for one hour. Dimethylformamide (0.88 ml, 11.4 mmol) was added dropwise and the mixture was stirred an additional 2 hours at −78° C. The reaction was quenched via the addition of 1N aqueous hydrochloric acid and allowed to warm to room temperature. The resulting biphasic mixture was extracted twice with ethyl acetate. The combined organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (silica, 0-17% ethyl acetate/hexanes) to afford the title compound.

Provenance & Evidence