Ethanol → Ethyl 2,6-dichloro-5-fluoropyridine-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

2,6-Dichloro-5-fluoropyridine-3-carboxylic acid (5.00 g, 23.81 mmol) was mixed with ~13 mL of thionyl chloride under nitrogen. The reaction was heated and the excess thionyl chloride was distilled off. The resulting liquid was diluted with ~5 mL methylene chloride, cooled to 0° C. and treated with 4.98 mL (1.5 equivalents) of triethylamine followed by 2.79 mL (2.0 equivalents) of ethanol dropwise. The reaction was allowed to warm to ambient temperature and stirred for 1 hour. A 1:1 mixture of sodium bicarbonate solution and ether (~80 mL) was added and the organic layer was washed with saturated sodium bicarbonate solution, 1N phosphoric acid and brine, dried over magnesium sulfate and concentrated in vacuo. The residue obtained was flash chromatographed on silica gel eluting with 5% ethyl acetate in hexane to give the title compound (5.32 g, 94%) as a yellow liquid. 1H NMR (CDCl3, 300 MHz) δ 1.42 (t, 3 H), 4.43 (q, 2H), 8.00 (d, 1H). MS (DCl/NH3) m/e 239 (M+H)+.

Provenance & Evidence