Hydrochloric Acid → 1-Methyl-3-(1-methylethyl)-5-(methyloxy)-1H-indole-7-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To methyl 5-bromo-1-methyl-3-(1-methylethyl)-1H-indole-7-carboxylate (620 mg, 2 mmol) and Copper(I)iodide (476 mg, 2.500 mmol) was added N-Methyl-2-pyrrolidone (NMP) (4 mL). To the mixture was added dropwise a solution of sodium methoxide (in methanol) (1802 mg, 8.34 mmol) with stirring over a 5 min period, during which time contents turned dark green. The reaction was heated to 120° C., upon which the contents were nearly black colored. The black colored mixture was stirred at 120° C. After 1 h 45 min, the dark reddish brown colored contents were removed from heating and allowed to cool. Upon reaching 80° C., water (150 uL) was added and the reaction mixture was allowed to cool to room temperature with stirring overnight. The reaction contents were then acidified with 1N HCl (8 mL), upon which the contents became a brown suspension. The mixture was diluted with water (8 mL), and lightened a bit. Next added EtOAc (10 mL), and the contents become a biphasic mixture. The contents were filtered through Celite, and the filter cake was washed with EtOAc. The filtrate was poured into a separatory funnel, and the organic phase was separated and set aside. The aq. phase was extracted with EtOAc (2×10 mL), and combined with the previously saved organic layer. The combined organic layers were washed with brine (10 mL), dried (MgSO4), filtered, and concentrated under vacuum. Purification by silica gel chromatography (gradient: 10 to 50% EtOAc in hexanes) gave the title compound as a cream colored solid (80 mg, 16%). Note: Some material loss occurred during purification due to a collection malfunction. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.28 (d, J=6.82 Hz, 6H), 3.08-3.16 (m, 1H), 3.74 (s, 3H), 3.80 (s, 3H), 7.09 (s, 2H), 7.21 (s, 1H), 12.9-13.1 (br s, 1H). MS(ES) [M+H]+ 248.2.

Provenance & Evidence