Cesium fluoride → Methyl 3,4-dichloro-6-acetylpyridine-2-carboxylate

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Reaction Conditions

Reaction Steps

A solution of methyl 3,4,6-trichloropyridine-2-carboxylate (2.00 g, 8.31 mmol), ethoxyvinyltributyltin (3.09 mL, 9.15 mmol) and cesium fluoride (2.78 g, 18.30 mmol) in dioxane (50 mL) was sparged with nitrogen for 15 minutes. Dichlorobis(triphenylphosphine) palladium(II) (292 mg, 0.42 mmol) was then added and the mixture heated at 100° C. for 3 hours. After cooling, the mixture was concentrated, taken up into ethyl acetate and was filtered through a silica gel plug. The solvent was removed and the crude ethoxyvinyl intermediate was then dissolved in a solution of tetrahydrofuran (50 mL) and 1N HCl acid (20 mL). After stirring the mixture at room temperature overnight, the tetrahydrofuran was removed in vacuo and the remaining aqueous phase extracted with ethyl acetate. The organic layers were combined, dried (MgSO4), and concentrated. Purification by column chromatography (10% ethyl acetate in hexane) provided methyl 3,4-dichloro-6-acetylpyridine-2-carboxylate (0.98 g, 3.95 mmol) as a white solid; 1H NMR (CDCl3): δ 8.20 (s, 1H), 4.05 (s, 3H), 2.71 (s, 3H).

Provenance & Evidence