1,2-Dibromoethane → 5-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine

To a solution of 2-amino-m-cresol (5.0 g) in N,N-dimethylformamide (50 ml), potassium carbonate (28.3 g) and 1,2-dibromoethane (5.3 ml) were added and stirred at 130° C. for 4 hours and then stirred overnight at room temperature. To the reaction mixture, 1,2-dibromoethane (5.3 ml) was added and stirred at 130° C. for 6 hours. After addition of additional 1,2-dibromoethane (3.5 ml), the reaction mixture was stirred at 130° C. for 5 hours and then stirred overnight at room temperature. After insoluble materials were filtered off, the filtrate was diluted with ethyl acetate and washed sequentially with water and brine. The organic layer was dried over anhydrous sodium sulfate and then filtered to remove the desiccant, followed by distilling off the solvent under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=20:1 to 10:1) to give the titled compound, i.e., 5-methyl-3,4-dihydro-2H-1,4-benzoxazine (2.69 g) as a brown oil.

1. stirringstirred overnight at room temperature
2. stirringstirred at 130° C. for 6 hours
3. stirringthe reaction mixture was stirred at 130° C. for 5 hours
4. stirringstirred overnight at room temperature
5. filtrationAfter insoluble materials were filtered off
6. additionthe filtrate was diluted with ethyl acetate
7. washwashed sequentially with water and brine
8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
9. filtrationfiltered
10. customto remove the desiccant
11. distillationby distilling off the solvent under reduced pressure
12. customThe resulting residue was purified by silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=20:1 to 10:1)

ORD record

ord-55534882ddbb4533889b103442d9e50d

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08222417B2