2-Methyl-2-butene → 6-Chloro-5-(4-(1-(hydroxymethyl)cyclobutyl)phenyl)-1h-indole-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a mixture of 6-chloro-5-{4-[1-(hydroxymethyl)cyclobutyl]phenyl}-1H-indole-3-carbaldehyde (80 mg, 0.24 mmol) in acetonitrile (6 mL) and tert-butanol (6 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 hydrate (650 mg, 4.80 mmol) in water (3 mL) dropwise via additional funnel. The ice bath was removed, and the reaction mixture was stirred at room temperature for 24 hours. The solvent was removed in vacuo to give a residue, which was purified by prep-HPLC (Kromasil Eternity-5-C18 150*30 mm*5 μm Mobile phase: from 35% MeCN in water (0.1% TFA) to 50% MeCN in water (0.1% TFA); Wavelength: 220 nm Flow rate: 30 mL/min) to give 6-chloro-5-{4-[1-(hydroxymethyl)cyclobutyl]phenyl}-1H-indole-3-carboxylic acid (25 mg, 32% yield) as a white solid. MS (ES+) 377.9 (M+Na)+. 1H NMR (400 MHz, CD3OD) δ 8.01 (s, 1H), 7.97 (s, 1H), 7.57 (s, 1 H), 7.39 (d, 2 H), 7.23 (d, 2 H), 3.70 (s, 2H), 2.39-2.30 (m, 4 H), 2.11-2.09 (m, 1 H), 1.92-1.91 (m, 1 H).

Provenance & Evidence