2-Methyl-2-butene → 1-(4-Fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carboxylic acid

Participants

Reaction Steps

1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde (8 g, 23 mmol) and sodium phosphate monobasic (8 g, 58.4 mmol) were stirred vigorously in a mixture of THF (35 mL), tert-butanol (35 mL), and water (35 mL) at 0° C. 2-Methyl-2-butene (2.0 M in THF 36.1 mL, 72.2 mmol) was added to the reaction mixture, followed by sodium chlorite (4.8 g, 53.7 mmol). The ice bath was removed and the reaction mixture was warmed to RT and stirred vigorously for 1 h. 1N HCl (20 mL) was added. The mixture was stirred for 5 min. The solids were collected by filtration and washed with water, EtOAc, and ether. The layers of the filtrate were separated, the aqueous layer was extracted with EtOAc, and the combined organics were dried over MgSO4 and concentrated in vacuo. The resulting solid was suspended in EtOAc, filtered, and washed with EtOAc and ether to yield additional product. The pale yellow solids (8.22 g) were combined, dissolved in a minimal amount of 1N aqueous NaOH, treated with EtOAc, and stirred vigourously for 5 min. The layers were separated, and the aqueous layer was washed with EtOAc. The aqueous layer was acidified to pH 1 with conc HCl. The pale yellow solid that precipitated out of solution was collected by filtration, washed with water, EtOAc, and ether, and dried under vacuum to afford 1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carboxylic acid (5.4 g, 64.5% yield). 1H NMR (400 MHz, DMSO-d6): δ 13.5 (s, 1 H), 7.43-7.47 (m, 3 H), 7.30-7.35 (m, 2 H), 6.76 (d, J=7.2 Hz, 1 H).

Provenance & Evidence