Hydrochloric Acid → (S)-8-bromo-3-methyl-3,4-dihydroquinoxalin-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

To a 2-L, 3-necked round-bottomed flask equipped with a mechanical stirrer, nitrogen gas inlet, and temperature probe was sequentially added (S)-ethyl 2-((3-bromo-2-nitrophenyl)amino)-propanoate (50 g, 158 mmol), EtOH (750 mL), and iron powder (325 mesh, Aldrich; 39.6 g, 709 mmol). The resulting slurry was cooled to 0-5° C. on an ice water bath, and HCl (6.0 N, aq.; 342 mL, 2050 mmol) was added, dropwise, such that the internal reaction temperature did not exceed 5° C. After 1 h, brine (500 mL) and EtOAc (1500 mL) were added, such that the internal reaction temperature was kept below 10° C. The resulting mixture was vacuum filtered, and the collected solid was washed with EtOAc. The organic phase of the filtrate was separated and sequentially washed with brine (300 mL), saturated aq. NaHCO3 (500 mL; repeated until aq. layer pH ≧7), and EDTA trisodium salt solution (1 N, aq.; 300 mL). The organic layer was then concentrated in vacuo to provide (S)-8-bromo-3-methyl-3,4-dihydroquinoxalin-2(1H)-one (126c; 40.0 g, 165.9 mmol, 105% yield) as a light-brown oil, which was used without further purification in the subsequent step: m/z (ESI, +ve) 241.0 (M+H)+.

Provenance & Evidence