2-Methyl-2-butene → 5-{4-[2-(acetylamino)ethoxy]phenyl}-6-chloro-1H-indole-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of N-{2-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenoxy]ethyl}acetamide (80 mg, 0.23 mmol) in acetonitrile (3 mL) was added tert-butanol (3 mL) and 2-methyl-2-butene (1.89 mL). The reaction mixture was cooled to 0° C., and treated with a solution of sodium chlorite (452 mg, 6.74 mmol) and sodium phosphate monobasic (930 g, 6.74 mmol) in water (3 mL) dropwise. The reaction mixture was stirred at room temperature for 40 h. The reaction mixture was quenched with sodium sulfite and concentrated in vacuo to give a solid. The crude product was washed with DMF and the filtrate was concentrated in vacuo to give a brown residue, which was purified by prep-HPLC to give 5-{4-[2-(acetylamino)ethoxy]phenyl}-6-chloro-1H-indole-3-carboxylic acid (22 mg, 26%) as an off-white solid. MS (ES+) 373.1 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 11.93 (s, 1 H), 8.14 (br. s., 1 H), 8.06 (s, 1 H), 7.93 (s, 1 H), 7.62 (s, 1 H), 7.34 (d, 2 H), 7.02 (d, 2 H), 4.03 (t, 2 H), 3.45-3.43 (m, 2 H), 1.84 (s, 3 H).

Provenance & Evidence