Hydrochloric Acid → 1-(4-Fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carboxylic acid

Participants

Reaction Steps

A 0° C. mixture of 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) in 1:1:1 THF/t-BuOH/water (105 mL) was treated with 2-methyl-2-butene (2.0 M in THF, 36.1 mL, 72.2 mmol) followed by sodium chlorite (4.8 g, 53.7 mmol) and the vigorously stirred mixture warmed to RT and stirred for 1 h. HCl (1 M, 20 mL) was added, the mixture stirred for 5 minutes and the solid was collected via filtration and washed with water, EtOAc, then Et2O. The layers of the filtrate were separated and the aqueous layer extracted with additional EtOAc. The combined organics were dried over MgSO4, concentrated to dryness, the residue suspended in EtOAc, the solid collected via filtration and combined with the above-isolated solid. The combined material was dissolved in a minimum amount of 1N NaOH, treated with EtOAc, stirred vigorously for 5 minutes and the layers separated. The aqueous layer was washed with EtOAc, acidified to pH=1 with conc. HCl and the resulting solid was collected via filtration, washed with water, EtOAc and Et2O and dried to afford 1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carboxylic acid (5.4 g, 65%). 1H NMR (400 MHz, DMSO-d6): δ 13.5 (brs, 1H), 7.43-7.47 (m, 3H), 7.30-7.35 (m, 2H), 6.76 (d, J=7.2 Hz, 1H).

Provenance & Evidence