2-Methyl-2-butene → 6-Chloro-5-(4-methoxy-phenyl)-1H-indole-3-carboxylic acid

Participants

Reaction Steps

To a solution of 6-chloro-5-(4-methoxy-phenyl)-1H-indole-3-carbaldehyde (27.7 g, 97 mmol) in MeCN (400 mL), tert-butanol (400 mL) and 2-methyl-2-butene (400 mL, 3.76 mol) at 0° C. was added a solution of sodium chlorite (82.0 g, 970 mmol) and sodium phosphate monobasic hydrate (134.0 g, 970 mmol) in water (400 mL) dropwise over 20 minutes. The ice bath was removed and the mixture was stirred at room temperature. At the 16-hour and 20-hour time points, additional 2-methyl-2-butene (200 mL, 1.88 mol) was added, followed by solid sodium chlorite (82.0 g, 970 mmol) and solid sodium phosphate monobasic hydrate (134.0 g, 970 mmol). After a total of 22 hours, the reaction mixture was poured into a solution of saturated NH4Cl (800 mL) and water (200 mL), then extracted with EtOAc (4×500 mL). The combined organic layers were dried over MgSO4, and concentrated in vacuo to afford 62 g of a mustard-colored semi-solid. This solid was triturated in CHCl3 (70 mL), filtered and dried under high vacuum to afford 18.5 g pale yellow solid. The solid was stirred in EtOAc (50 mL) overnight at 55° C., then filtered hot and washed with room temperature EtOAc to afford the title compound (19.5 g, 63% for 2 steps) as a pale yellow solid. MS (ES+) 302.5 (M+H)+. 1H NMR (500 MHz, DMSO-d6) δ 12.10 (br. s., 1H), 11.93 (br. s., 1H), 8.07 (d, J=2.68 Hz, 1H), 7.93 (s, 1H), 7.62 (s, 1H), 7.35 (d, J=8.54 Hz, 2H), 7.01 (d, J=8.78 Hz, 2H), 3.81 (s, 3H).

Provenance & Evidence