Methyl iodide → Methyl 1-methyl-1H-indole-4-carboxylate

Participants

Reaction Steps

To a stirring suspension of sodium hydride (60% dispersion in mineral oil, 9.90 g, 248 mmol) in DMF (150 mL) was slowly added a solution of methyl indole-4-carboxylate (10.0 g, 62.1 mmol) in DMF (100 mL) at room temperature under an atmosphere of nitrogen. The mixture stirred for 30 minutes, then iodomethane (15.4 mL, 248 mmol) was added and the mixture continued to stir at room temperature for an additional 16 hours. The mixture was quenched with a saturated solution of ammonium chloride (500 mL) and the aqueous mixture was extracted with ethyl acetate (3×300 mL). The combined organic layers were washed with water (4×300 mL) and brine (200 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification of the resulting residue by column chromatography (0% to 30% ethyl acetate in hexanes) afforded methyl 1-methyl-1H-indole-4-carboxylate (Ala, 10.56 g, 90%) as an oil, which crystallized upon standing: 1H NMR (500 MHz, CDCl3) δ 7.91 (d, J=1.7 Hz, 1H), 7.48 (d, J=1.6 Hz, 1H), 7.21 (m, 1H), 7.14 (s, 1H), 7.09 (s, 1H), 3.96 (s, 3H), 3.75 (s, 3H); MS (ESI+) m/z 190 (M+H).

Provenance & Evidence