Hydrochloric Acid → 3-ethyl-7-fluoro-3,4-dihydroquinoxalin-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

The heterogeneous mixture of 2-(4-fluoro-2-nitrophenylamino)butanoic acid (181.7 g, 750.0 mmol), 3 N aq. HCl (750.0 ml, 2250 mmol), and ethanol (1923 ml, 750.0 mmol) in 5-L three neck round bottom flask was added Tin(II) chloride dihydrate (507.7 g, 2250 mmol) and the organe mixture was heated at 78° C. with stirring using an overhead stirrer for 4 h ([Note 1]: The orange heterogeneous mixture became an orange homogeneous mixture and the orange color changed to a red color over ˜2 hour). After 4 h, the mixture was cooled to rt and concentrated under reduced pressure to remove ethanol, and left at rt for 48 h. The resulting yellow precipitate was collected by filtration and washed with water (500 mL). The yellow solid was suspended in ice water (1 L) and the mixture was adjusted ˜pH 13 with KOH (˜250 g). The heterogeneous mixture was extracted with DCM (1 L×3). The combined organic layers were washed with water (1 L×1) and brine (1 L×1), dried over Na2SO4, filtered, and concentrated under reduced pressure to give 3-ethyl-7-fluoro-3,4-dihydroquinoxalin-2(1H)-one (60.92 g, 41.8% yield) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.26 (s, 1H), 6.68 (dd, J=8.6, 5.5 Hz, 1H), 6.47-6.61 (m, 2H), 5.95 (d, J=1.2 Hz, 1H), 3.62 (ddd, J=6.7, 5.0, 2.0 Hz, 1H), 1.50-1.72 (m, 2H), 0.92 (t, J=7.4 Hz, 3H), Mass Spectrum (ESI) m/e=195.1 (M+1).

Provenance & Evidence