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

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-chloro-5-[4-(5-oxomorpholin-2-yl)phenyl]-1H-indole-3-carbaldehyde (150 mg, 0.42 mmol) in acetonitrile (5 mL) and t-BuOH (5 mL) was added 2-methyl-2-butene (2.9 g, 42 mmol). The mixture was cooled to 0° C. with ice bath. Sodium chlorite (1.15 g, 12.7 mmol) and sodium phosphate monobasic hydrate (1.75 g, 12.7 mmol) were dissolved in water (5 mL). The aqueous was added to the organic solution and the mixture was allowed to warm to room temperature. The reaction mixture was stirred at room temperature for 48 hours. A solution of sodium sulfite was added slowly to the stirring mixture. The reaction mixture was allowed to stir 1 hour. Then the organics were removed under reduced pressure. The aqueous layer was extracted with ethyl acetate (10 mL×3). The combined organic layers was dried over sodium sulfate, filtered, and concentrated in vacuo to give a brown residue. The residue was purified by reverse phase HPLC to give the title compound (40 mg, 26% yield) as an off-white solid. MS (ES+) 371.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 12.00 (s, 1H), 8.20 (s, 1H), 8.10 (s, 1H), 7.93 (s, 1H), 7.63 (s, 1H), 7.48 (d, 2H), 7.44 (d, 2H), 4.65 (m, 1H), 4.22 (s, 2H), 3.46 (m, 2H).

Provenance & Evidence