N-bromobutanimide → 2-Bromo-1-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)ethanone

Participants

Reaction Steps

To a stirred solution of 1-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)ethanone (606a) (14.96 g, 58.1 mmol) and TEA (12.15 mL, 87 mmol) in DCM (100 mL) at 0° C. was added tert-butyldimethylsilyl trifluoromethanesulfonate (13.18 mL, 57.4 mmol) dropwise. After the addition, the reaction mixture was stirred at RT for 3 h. It was cooled with an ice bath and quenched with 50 mL of saturated NaHCO3. The layers were separated. The aq. layer was extracted with DCM (2×50 mL). The combined DCM extracts were dried over Na2SO4 and concentrated. The remaining light brown oil was dissolved in THF (100 mL) and H2O (10 mL), cooled with an ice bath, and treated with NBS (10.35 g, 58.1 mmol) in a single portion. The resulting mixture was stirred at 0° C. for 2 h, quenched with 50 mL of saturated NaHCO3, and extracted with EtOAc (3×100 mL). The organic extracts were combined, washed with 20 mL of brine, dried over MgSO4 and concentrated. The resulting yellow solid was treated with 100 mL of MeOH and stirred for 10 min. The yellow solid was filtered, rinsed with MeOH (2×5 mL), collected and dried in a vacuum oven at RT for 18 h to give 2-bromo-1-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)ethanone (606) (15.5 g, 79% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.91 (1H, dd, J=8.0, 1.6 Hz), 7.75 (1H, dd, J=7.3, 1.5 Hz), 7.41 (1H, t, J=7.6 Hz), 6.18 (1H, s), 5.15 (2H, s), 2.58 (3H, s), 1.52 (9H, s). m/z (ESI, +ve) 336/338 (M+H)+.

Provenance & Evidence