Citric Acid → 2-Difluoromethyl-3-fluoro-isonicotinic acid

Participants

Reaction Steps

To a solution of methyl 2-(difluoromethyl)-3-fluoroisonicotinate (0.44 g, 2.1 mmol, from Step 4) in tetrahydrofuran (10 mL) was added a solution of lithium hydroxide monohydrate (0.45 g, 11 mmol) in water (10 mL). The reaction was stirred for 2 hours. The reaction mixture was acidified by the addition of a solution of citric acid. The product was extracted with three portions of DCM. The combined extracts were dried over sodium sulfate, decanted and concentrated to afford product, which was used without further purification in Step 6. H NMR (300 MHz, CD3OD): δ 8.57 (d, 1H), 7.99 (dd, 1H), 6.96 (t, 1H).

Provenance & Evidence