Methyl iodide → Methyl N-methylindole-6-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of 1H-indole-6-carboxylic acid (2.60 g, 16.1 mmol) in tetrahydrofuran (100 mL) and diethyl ether (100 mL) was treated with ethereal diazomethane until tlc indicated complete consumption of the starting material. After the solution was allowed to stand overnight, the solvent was evaporated under reduced pressure and the resulting residue was dissolved in tetrahydrofuran (100 mL). The solution was cooled to ˜0° C. and sodium hydride (60% suspension in mineral oil; 2.00 g, 50.0 mmol) and then iodomethane (10.00 g, 70.5 mmol) were added. and the reaction mixture was stirred at room temperature overnight. Water (200 mL) was added, carefully at first and the mixture was extracted with ethyl acetate (2×200 mL). The combined ethyl acetate layers were washed with brine (100 mL), dried (MgSO4), filtered and concentrated in vacuo. The crude product was chromatographed over silica gel (30-50% ethyl acetate/hexanes) to furnish 1-methyl-1H-indole-6-carboxylic acid methyl ester (2.52 g, 83% yield) as a yellow oil that solidified on standing.

Provenance & Evidence