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

Temperature

95 °C

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)+.

1. additionwas added slowly at RT over 3 hours
2. additionWhen the addition
3. temperaturethe reaction was heated
4. temperatureat reflux for 3 hr
5. filtrationhot-filtered through a pad of Celite®
6. washThe filter pad was washed with hot MeOH (500 mL)
7. concentrationthe filtrate was concentrated in vacuo
8. customWhen most of the MeOH was removed
9. filtrationthe mixture was filtered
10. customto collect the solid, which
11. washwas washed with water (100 mL)
12. extractionThe filtrate was extracted with CHCl3 (300 mL, 2 times)
13. washthe organic layer was washed sequentially with water and brine
14. dry with materialdried (MgSO4)
15. concentrationconcentrated in vacuo
16. filtrationThe residue was combined with the solid from the filtration
17. concentrationThe mixture was then concentrated in vacuo
18. customthe residue was triturated with Et2O (200 mL)
19. customThe solid was collected
20. washwashed with ether
21. customdried

ORD record

ord-959d4281d3b44d718ad14d0d315ee087

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07709496B2