Methyl chloroformate → Methyl 6-chloro-2-fluoronicotinate

Participants

Reaction Conditions

Reaction Steps

2-Chloro-6-fluoropyridine (298 mg, 2.3 mmol) was taken up in tetrahydrofuran (11.4 mL) and cooled to −78° C. n-Butyllithium (1.42 mL of 1.6 M in hexanes, 2.3 mmol) was added dropwise over 5 min. The solution was stirred for 30 minutes and methyl chloroformate (0.3 mL, 3.9 mmol) was added dropwise over 15 minutes. The resulting mixture was stirred at −78° C. for 2 hrs and then warmed to 0° C. and stirred for 3 hours. The reaction was then quenched with saturated aqueous ammonium chloride and extracted 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 as a white solid.

Provenance & Evidence