Butyl Acrylate → 6-Phenylmethoxy-1,2-dihydropyrrolo[1,2-a]indol-3-one

Participants

Reaction Conditions

Reaction Steps

Ethyl 5-(benzyloxy)-1H-indole-2-carboxylate (25 g, 85 mmol) was dissolved in toluene (125 mL) and 60% sodium hydride in mineral oil (7.79 g, 195 mmol) was added portionwise. The reaction was stirred for 50 min and butyl acrylate (26.6 mL, 186 mmol) was added. The reaction was stirred at room temperature for 1.5 h and additional butyl acrylate (20 mL) was added. After stirring for 30 min, the solution was warmed to 70° C. and stirred for 1 h. The reaction was cooled to room temperature and sodium hydride (4.0 g) was added. The reaction was warmed to 70° C. causing the reaction to reflux. The heat source was removed and butyl acrylate (15 mL) was added and heating at 70° C. was resumed. After 30 min, the heat source was removed and the reaction was left to stir for 16 h. Water (25 mL) was added followed by 1.0 M HCL (250 mL) and 12 M HCL (50 mL). The aqueous layer was removed and the toluene was washed two times with water (100 mL). The toluene layer was concentrated under reduced pressure and the concentrate was taken up in acetic acid (120 mL) and water (12 mL). The reaction mixture was heated under reflux and stirred for 24 h. The reaction mixture was cooled to room temperature and water (200 mL) was added. The aqueous mixture was diluted with ethyl acetate and washed with water and brine. The ethyl acetate layer was filtered through a pad of Celite® and the filtrate was concentrated under reduced pressure. The residue was purified by crystallization from methanol to provide the title compound (8.0 g). LCMS m/z=278.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 3.20 (t, J=6.6 Hz, 2H), 4.41 (t, J=6.2 Hz, 2H), 5.11 (s, 2H), 6.91 (s, 1H), 7.13 (dd, J=9.0, 2.4 Hz, 1H), 7.19 (d, J=2.4 Hz, 1H), 7.30-7.42 (m, 4H), 7.44-7.49 (m, 2H).

Provenance & Evidence