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

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-chloro-5-{4-[2-(morpholin-4-yl)-2-oxoethyl]phenyl}-1H-indole-3-carbaldehyde (249 mg, 0.650 mmol) in acetonitrile (6 mL) and tert-butanol (6 mL) was added 2-methyl-2-butene (4 mL). The reaction mixture was cooled to 0° C. and treated with a solution of sodium chlorite (880 mg, 13.1 mmol) and sodium phosphate monobasic dihydrate (2030 mg, 13.01 mmol) in water (3 mL) via addition funnel. The icebath was removed and the mixture was allowed to warm to room temperature. The reaction mixture was stirred at room temperature for 18 hours. The reaction was quenched with aqueous sodium sulfite, concentrated in vacuo and extracted with ethyl acetate (4×25 mL). The combined organic phases were washed with brine (20 mL), dried and concentrated in vacuo. The crude product was purified by prep-HPLC (Column: Phenomenex Synergi C18 150*30 mm*4 μm; Mobile phase: from 38% MeCN in water (0.225% FA) to 58% MeCN in water (0.225% FA); Wavelength: 220 nm) to afford the title compound (65 mg, 28% yield) as a white solid. MS (ES+) 399.0 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 8.03 (s, 1H), 8.01 (s, 1H), 7.59 (s, 1H), 7.43 (d, 2H), 7.34 (d, 2H), 3.87 (s, 2H), 3.65 (m, 4H), 3.52 (m, 2H), 3.55 (m, 2H).

Provenance & Evidence