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

Participants

Reaction Conditions

Reaction Steps

To a mixture of 6-chloro-5-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-1H-indole-3-carbaldehyde (80 mg, 0.24 mmol) in acetonitrile (3 mL) and tert-butanol (3 mL) was added 2-methyl-2-butene (3 mL). The reaction mixture was cooled to 0° C. and treated with a solution of sodium chlorite (420 mg, 4.80 mmol) and sodium phosphate monobasic (650 mg, 4.80 mmol) in water (3 mL) dropwise via addition funnel. The reaction mixture was warmed to room temperature and stirred for 20 hours. The solvent was removed in vacuo to give a residue, which was purified by prep-HPLC (Column: Boston Symmetrix ODS-H 150*30 mm*5 μm Mobile phase: from 36% MeCN in water (0.1% TFA) to 36% MeCN in water (0.1% TFA); Wavelength: 220 nm Flow rate: 30 mL/min) to give 6-chloro-5-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-1H-indole-3-carboxylic acid (25 mg, 32% yield) as a white solid. MS (ES+) 364.0 (M+Na)+. 1H NMR (400 MHz, DMSO-d6) δ 12.13 (s, 1H), 11.96 (s, 1H), 8.07 (d, 1H), 7.92 (s, 1H), 7.62 (s, 1H), 7.38-7.32 (m, 4H), 4.73-4.71 (m, 1H), 3.58-3.57 (m, 2H), 0.88-0.77 (m, 4H).

Provenance & Evidence