Benzaldehyde → HCID 58310981, compound

Participants

Reaction Conditions

Reaction Steps

A 250 ml round bottom flask equipped with a stir bar and an addition funnel was charged with sodium cyanide (1.386 g, 28.3 mmol) and DMF (20 ml). The flask was placed in an oil bath at 35° C. To this suspension at 35° C., was added over the course of 30 minutes, solution of benzaldehyde (5.55 ml, 54.8 mmol) in DMF (20.00 ml). The mixture was stirred at 35° C. for an additional 1.5 h. To this mixture, was added over the course of 2 hours, a solution of (E)-4-(3-fluorophenyl)but-3-en-2-one (6.92 g, 42.1 mmol) in DMF (20 ml). The mixture was stirred at 35° C. overnight. The mixture was quenched with water (100 ml×2) and extracted with ethyl acetate (200 ml). The organic layer was washed with water (100 ml×3) and brine (100 ml). The combined organic layers were dried, filtered, and evaporated to give an oil. The oil was combined with ethyl 2-aminoacetate hydrochloride (4.03 g, 28.9 mmol), triethylamine (6.03 ml, 43.3 mmol) and EtOH (26.2 ml) and the resulting mixture was heated at 100° C. for 18 hours. It was then allowed to cool to room temperature and ethanol was removed. The residue was taken up in ethyl acetate (200 ml) and water (50 ml) and the organic layer was washed with water (100 ml×4). The organic layer was dried, filtered, and evaporated to give an oil which was further purified by column chromatography on silica gel (0 to 40% ethyl acetate in hexanes) to give ethyl 2-(3-(3-fluorophenyl)-5-methyl-2-phenyl-1H-pyrrol-1-yl)acetate (1.74 g, 5.16 mmol, 17.87% yield). 1H NMR (CDCl3/400 MHz): δ (ppm) 7.61-7.51 (m, 2H), 7.49-7.40 (m, 3H), 7.40-7.35 (m, 3H), 7.34-7.31 (m, 1H), 6.23 (d, 1H), 4.41 (s, 2H), 4.20 (q, 2H), 2.26 (d, 3H), 1.25 (t, 2H). MS m/z: 338.2 (M+1).

Provenance & Evidence