ethyl 3-hydroxypicolinate

To 3-hydroxypyridine-2-carboxylic acid (25 g, 179.5 mmol) in a 1 L dried flask was added 400 mL ethanol and 100 mL toluene followed by the addition of 10 mL sulfuric acid. The mixture was heated at reflux (95° C.) for 3 days. After cooling to rt, the mixture was concentrated to 1/4 of its volume, and diluted with 600 mL ethyl acetate and 200 mL water. The aqueous layer was extracted with 200 mL ethyl acetate, and the combined organic layers were washed with sat NaHCOTo 3-hydroxypyridine-2-carboxylic acid (25 g, 179.5 mmol) in a 1 L dried flask was added 400 mL ethanol and 100 mL toluene followed by the addition of 10 mL sulfuric acid. The mixture was heated at reflux (95° C.) for 3 days. After cooling to rt, the mixture was concentrated to 1/4 of its volume, and diluted with 600 mL ethyl acetate and 200 mL water. The aqueous layer was extracted with 200 mL ethyl acetate, and the combined organic layers were washed with sat NaHCOA solution of 3-hydroxypicolinic acid (2.50 g, 18.0 mmol) in EtCH (60 mL) and toluene (20 mL) was treated with conc. H2S04 (1 mL) and stirred under reflux for 60 h withazeotropic removal of water via Dean-Stark trap. The solvent was evaporated, the residue was dissolved in water (50 mL) and carefully basified with a sat. NaHCO3 solution, upon which a white precipitate appeared. The mixture was diluted with EtOAc (30 mL) and the aqueous layer was extracted three times with EtOAc (3 x 20 mL). The combined organic layers were dried over anhydrous Mg504, filtered and evaporated to giveethyl 3-hydroxypicolinate (2.10 g, 70percent) as a colorless liquid.1H NMR (400 MHz, Chloroform-o) 6 = 10.78 (s, 1H, OH), 8.30 (dd, J= 4.2, 1.5 Hz, 1H, H-Ar), 7.47 — 7.34 (m, 2H, H-Ar), 4.54 (q, J= 7.1 Hz, 2H, O-CH2CH3), 1.49 (t, J= 7.1Hz, 3H, O-CH2CH3) ppm.MS (ESl+, H20/MeCN) mlz(percent): 168.0 (100, [M + H]j.