Methanol → Methyl 5-fluoropyridine-2-carboxylate

Participants

Reaction Steps

A mixture of 2-bromo-5-fluoropyridine (72.5 g, 412 mmol), palladium(II) acetate (2.5 g, 11.2 mmol), 1,1′-bis(diphenylphosphino)ferrocene (11.9 g, 21.5 mmol), triethylamine (100 mL), CH3OH (350 mL), and DMF (350 mL) were shaken in a pressure apparatus at 80° C. under 4.1 bar (60 psig) carbon monoxide overnight. The crude mixture was diluted with ether (3 L) and filtered through diatomaceous earth. The filtrate was washed with brine (3×500 mL), dried (Na2SO4), filtered and the solvent removed. Flash chromatography, using 10–25% ethyl acetate in hexanes, afforded 26.2 g (169 mmol, 41% yield) of methyl 5-fluoropyridine-2-carboxylate.

Provenance & Evidence