Acetic Anhydride → 1-(5-Methoxyindolin-1-yl)ethanone

Participants

Reaction Steps

A 4-neck 22L round bottom flask equipped with a reflux condenser, mechanical stirrer and thermowell was charged with 5-methoxyindoline (1520 g, ca. 10.2 mol) produced in accordance with Step A, immediately above and dichloromethane (15 L). To the solution was added 4-dimethylaminopyridine (50 g, 0.446 mol), followed by slow addition of acetic anhydride (1051 mL, 11.22 mol, 1.1 equiv, maintaining gentle reflux of the solvent). The reaction mixture was stirred at room temperature overnight. After completion, the reaction mixture was diluted with dichloromethane (10 L), then washed with water (15 L) and saturated sodium bicarbonate solution (15 L). The organic layer was dried over sodium sulfate and evaporated in vacuo to a crude solid, which was triturated from heptane (4 L) to afford 1-acetyl-5-(methyloxy)-2,3-dihydro-1H-indole (1800 g, 92% yield over two steps). 1H-NMR (CDCl3, 300 MHz) δ 8.13 (d, J=6.3 Hz, 1H), 6.74-6.71 (m, 2 H), 4.05 (t, 2 H), 3.78 (s, 3 H), 3.17 (t, 2 H), 2.21 (s, 3 H).

Provenance & Evidence