Ammonium Chloride → 6-Bromo-2H-pyrido[3,2-B][1,4]oxazin-3(4H)-one

Participants

Reaction Conditions

Reaction Steps

Ammonium chloride (44 g, 0.823 mole) was dissolved in H2O (600 mL), and iron powder (−325 mesh, 27.4 g, 0.491 mole) was added. The mixture was mechanically stirred (vigorously), and a solution of ethyl (6-bromo-2-nitro-pyridin-3-yloxy)acetate (50 g, 0.164 mole) in MeOH (800 mL) was added slowly at RT over 3 hours. When the addition was done, the reaction was heated at reflux for 3 hr and then hot-filtered through a pad of Celite®. The filter pad was washed with hot MeOH (500 mL) and the filtrate was concentrated in vacuo. When most of the MeOH was removed, the mixture was filtered to collect the solid, which was washed with water (100 mL). The filtrate was extracted with CHCl3 (300 mL, 2 times) and the organic layer was washed sequentially with water and brine, dried (MgSO4), and concentrated in vacuo. The residue was combined with the solid from the filtration, suspended in glacial AcOH (150 mL), and the mixture was heated at 95° C. for 3 hr. The mixture was then concentrated in vacuo and the residue was triturated with Et2O (200 mL). The solid was collected, washed with ether, and dried to afford the title compound (30 g, 80%): MS (ES) m/e 229.0 (M+H)+.

Provenance & Evidence