Sodium Sulfite → 4,6-difluoro-5-[4-(2-hydroxyethoxy)phenyl]-1H-indole-3-carboxylic acid

Participants

Reaction Steps

To a solution of 4,6-difluoro-5-[4-(2-hydroxyethoxy)phenyl]-1H-indole-3-carbaldehyde (70 mg, 0.221 mmol) in acetonitrile (4.6 mL), t-butanol (4.6 mL) and 2-methyl-2-butene (3.0 mL) was added a solution of sodium chlorite (298 mg, 4.42 mmol) and sodium dihydrogen phosphate (610 mg, 4.42 mmol) in water (4.6 mL) in an ice-bath. The reaction mixture was stirred at room temperature for 18 h. TLC (petroleum ether/EtOAc=1:1) showed the reaction was complete. The reaction was quenched with a solution of sodium sulfite (612 mg, 4.86 mmol) in water (5.0 mL), and extracted with ethyl acetate (20 mL×3). The organic layers were washed with brine (10 mL) and dried over sodium sulfate, filtered and concentrated to give a crude residue, which was purified by reverse phase HPLC to give the title compound (21.1 mg, 29%) as a white solid. MS (AP+) 333.9 (M+1)+. 1H NMR (400 MHz, CD3OD) δ 8.00 (s, 1H), 7.49 (d, 2H), 7.12 (d, 1H), 7.05 (d, 2H), 4.13 (t, 2H), 3.92 (t, 2H)

Provenance & Evidence