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

Temperature

100 °C

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).

1. temperatureAfter cooling
2. concentrationthe mixture was concentrated
3. filtrationwas filtered through a silica gel plug
4. customThe solvent was removed
5. dissolutionthe crude ethoxyvinyl intermediate was then dissolved in a solution of tetrahydrofuran (50 mL) and 1N HCl acid (20 mL)
6. customthe tetrahydrofuran was removed in vacuo
7. extractionthe remaining aqueous phase extracted with ethyl acetate
8. dry with materialdried (MgSO4)
9. concentrationconcentrated
10. customPurification by column chromatography (10% ethyl acetate in hexane)

ORD record

ord-c2e358563cad47b990d50ef2fd45f006

Source dataset

uspto-grants-2007_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07291580B2