2-Chloro-6-methoxyquinoxaline

Synthesis

924-44-7

102-51-2

55687-11-1

A toluene solution of 50% ethyl 2-oxoacetate (18.47 mL, 93 mmol) was slowly added dropwise to a solution of 4-methoxybenzene-1,2-diamine (10.73 g, 78 mmol) in ethanol (100 mL) at room temperature and the reaction was stirred. After completion of the reaction, the mixture was concentrated under reduced pressure and the residue was recrystallized from methanol to give a mixture of 6-methoxyquinoxalin-2(1H)-one and 7-methoxyquinoxalin-2(1H)-one (5.73 g, 32.50 mmol, 42% yield). Subsequently, the above mixture (5.67 g, 32.20 mmol) was dissolved in phosphoryl chloride (120 mL) and heated to reflux for 1 hour. At the end of the reaction, the excess phosphoryl chloride was evaporated under reduced pressure and the residue was quenched with ice water and the pH was adjusted to alkaline with sodium carbonate solution. The aqueous phase was extracted with ethyl acetate (3 x 200 mL), the organic layers were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: 0 to 5% ethyl acetate/hexane gradient elution) to afford the target compound 2-chloro-6-methoxyquinoxaline (2.21 g, 11.36 mmol, 35% yield).

References