Hydrochloric Acid → 2-(1-Methyl-1H-indol-3-yl)acetamide

Participants

Reaction Steps

A solution of indole-3-acetonitrile (10.0 g, 64.0 mmol) in DMF (50 mL) was added dropwise to a suspension of sodium hydride (3.33 g, 83.3 mmol) in DMF (20 mL) at room temperature. The resultant mixture was stirred for 30 minutes and was cooled to 0°-5° C., and a solution of methyl iodide (13.63 g, 96.0 mmol) in DMF (30 mL) was added dropwise. The reaction was allowed to warm and stir at room temperature for 3 hrs. The reaction was worked up extractively using EtOAc (300 mL) and aqueous 0.5 N HCl (400 mL) and the organic layer dried (MgSO4) and solvent removed in vacuo to give 16.34 g (>100%) of crude alkylated product that was carried on without purification as follows. The oil was combined with tetrabutylammonium bromide (4.13 g, 12.8 mmol) in CH2Cl2 (100 mL) and was cooled in an ice bath before a 30% aqueous solution of hydrogen peroxide (33 mL) was added followed by an aqueous 20% weight solution of NaOH (26 mL). The reaction was allowed to warm to room temperature and stir for 21 hours before being worked up extractively with CH2Cl2 (650 mL), aqueous 1N HCl (500 mL) and water (500 mL). The organic layer was dried (MgSO4) and solvent removed in vacuo to give a thick slurry to which was added hexanes (100 mL). This mixture was filtered using 1:1 CH2Cl2 : hexanes (100 mL) as a rinse to give 8.45 g (70%) of the titled product after drying. NMR. MS (FD) m/z=188 (M+, 100%). Anal. calc'd for C11H12N2O C, 70.19; H, 6.43; N, 14.88. Found C, 70.02; H, 6.17; N, 14.99.

Provenance & Evidence