Hydrochloric Acid → 4'-Acetyl-1'-methyl-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-one

Participants

Reaction Conditions

Reaction Steps

A 10 mL septum-capped microwave pressure tube was charged with 4′-bromo-1′-methyl-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.39 g, 1.0 mmol), palladium (II) acetate (0.022 g, 0.1 mmol), 1,3-bis(diphenylphosphino)propane (0.10 g, 0.25 mmol) and potassium carbonate (0.17 g, 1.2 mmol). The tube was capped and purged for 5 min with dry nitrogen, and butyl vinyl ether (0.52 mL, 4.0 mmol), N,N-dimethylformamide (2.0 mL) and water (0.2 mL) were added. The reaction mixture was heated for 1 h under microwave irradiation (100 W, 120° C.) and was allowed to cool to ambient temperature, poured into 10% v/v aqueous hydrochloric acid (5 mL) and stirred at ambient temperature for 1 h. The mixture was diluted with water (20 mL) and was neutralized with 2 M aqueous sodium carbonate. Ethyl acetate (20 mL) was added and the biphasic mixture was filtered through a pad of diatomaceous earth. The pad was washed with ethyl acetate (20 mL) and the filtrate was transferred to a separatory funnel. The aqueous phase was extracted with ethyl acetate (3×20 mL). The combined organic extracts were washed with water (3×20 mL) and brine (20 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography and eluted with a 0% to 100% gradient of ethyl acetate in hexanes, followed by recrystallization from dichloromethane/diethyl ether to afford 4′-acetyl-1′-methyl-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.264 g, 75%) as an off-white solid: mp 234-235° C. (dichloromethane/diethyl ether); 1H NMR (300 MHz, CDCl3) δ7.55-7.44 (m, 2H), 7.14-7.08 (m, 1H), 6.50 (s, 1H), 5.99 (s, 1H), 4.95-4.77 (m, 2H), 4.19-4.04 (m, 4H), 3.28 (m, 3H), 2.43 (m, 3H); 13C NMR (75 MHz, CDCl3) δ198.3, 178.6, 157.2, 145.4, 144.3, 137.4, 134.5, 130.6, 129.5, 124.4, 119.9, 112.1, 110.2, 98.9, 78.9, 64.5, 64.0, 59.4, 28.5, 27.0; MS (ES+) m/z 351.8 (M+1).

Provenance & Evidence