Chloroacetyl chloride → 2H-1,4-Benzoxazin-3(4H)-one,4-methyl-

HRID 2261076Notes

Reaction equation

HRID 2261076 reaction equation
[CH3:1][NH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[OH:9].C([O-])(O)=O.[Na+].Cl[CH2:16][C:17](Cl)=[O:18]>C(Cl)(Cl)Cl.O.CC(C)=O>[CH3:1][N:2]1[C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[O:9][CH2:16][C:17]1=[O:18]

Participants

7

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 69138o-(Methylamino)phenolHCID 516892Sodium Bicarbonate

Product 1

HCID 890322H-1,4-Benzoxazin-3(4H)-one,4-methyl-Yield 109.4%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

1 g of 2-(N-methylamino)-phenol were dissolved in chloroform, followed by the addition of 10 ml of sat. NaHCO3 in water. To this suspension was added slowly under vigorous stirring a solution of 1 g of 2-chloroacetylchloride in acetone. The reaction mixture was stirred for 2 hours at room temperature. The layers were separated. The organic layer was washed with water and dried over Na2SO4. After evaporating the solvent, the red oil was taken up in 30 ml DMF and 1 g of K2CO3 were added and the slurry was heated at 70° C. for additional 2 hours. The cyclization was followed by TLC. 200 ml of EtOAc were added and the organic layer was washed 3× with 0.1N HCl and 5× with brine. The remaining organic layer was dried over MgSO4 and filtrated. EtOAc was removed under reduced pressure affording 1.45 g of pure 4-methyl-4H-benzo[1,4]oxazin-3-one.

Workup

  1. additionTo this suspension was added slowly
  2. customThe layers were separated
  3. washThe organic layer was washed with water
  4. dry with materialdried over Na2SO4
  5. customAfter evaporating the solvent
  6. addition1 g of K2CO3 were added
  7. temperaturethe slurry was heated at 70° C. for additional 2 hours
  8. addition200 ml of EtOAc were added
  9. washthe organic layer was washed 3× with 0.1N HCl and 5× with brine
  10. dry with materialThe remaining organic layer was dried over MgSO4
  11. filtrationfiltrated
  12. customEtOAc was removed under reduced pressure

Sources & evidence

ORD record
ord-007d2dff6d7a4fb9b63757c4f24c4c34
Source dataset
uspto-grants-2010_12
Patent number
US07846925B2

Reaction notes

Loading…