Phosphorus oxychloride → 5-Bromo-3-chloro-2-methylquinoxaline

Participants

Reaction Conditions

Reaction Steps

A slurry of 8-bromo-3-methylquinoxalin-2(1H)-one (6.33 g, 26.5 mmol) in phosphorus oxychloride (20 mL, 219 mmol) was heated at reflux for 1.5 h in a round-bottomed flask fitted with a water-cooled reflux condenser and drying tube. Excess POCl3 was removed in vacuo (16 Torr, 36° C.), and the residue was taken up in DCM (50 mL), transferred to an Erlenmeyer flask, cooled to 0° C., and saturated aq. NaHCO3 (ca. 80 mL) was added (cautiously, with rapid stirring). The resulting biphasic mixture was stirred rapidly for 5 min. Upon cessation of gas evolution, the mixture was extracted with DCM (3×200 mL), and the combined extracts were dried over Na2SO4, filtered, and concentrated onto silica gel. Chromatographic purification of the residue (silica gel, 0-30% EtOAc/hexanes) furnished 5-bromo-3-chloro-2-methylquinoxaline (126e; 5.12 g, 19.85 mmol, 75% yield) as a light-yellow solid: 1H NMR (400 MHz, CDCl3) δ ppm 8.02 (1H, d, J=7.6 Hz), 8.00 (1H, dd, J=8.4, 1.2 Hz), 7.60 (1H, t, J=7.9 Hz), 2.87 (3H, s). m/z (ESI, +ve) 256.9 (M+H)+.

Provenance & Evidence