Ethyl Acetate → 2-butyl-7-methoxycarbonyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine

HRID 234902Notes

Reaction equation

HRID 234902 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([O:10][CH3:11])=[O:9])=[CH:4][C:3]=1[OH:12].C(OCC)(=O)C.C(=O)([O-])O.[Na+].Br[CH:25]([CH2:29][CH2:30][CH2:31][CH3:32])[C:26](Br)=[O:27]>O>[CH2:29]([CH:25]1[C:26](=[O:27])[NH:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]([O:10][CH3:11])=[O:9])=[CH:4][C:3]=2[O:12]1)[CH2:30][CH2:31][CH3:32]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 30169232-Bromohexanoyl bromideHCID 7020619Benzoic acid, 4-amino-3-hydroxy-, methyl ester

Product 1

HCID 105394732-butyl-7-methoxycarbonyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazineYield 81.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 2-amino-5-methoxycarbonylphenol [Tetrahedron, 4.6 (15), 5177-5186 (1990)] (8.0 g) in a mixed solvent of ethyl acetate (200 ml) and water (200 ml) were added sodium hydrogen carbonate (11.18 g) and 2-bromohexanoyl bromide (12.73 g) and the mixture was stirred at room temperature for 10 minutes. The organic layer was separated and the solvent was distilled off under reduced pressure. The resulting residue was dissolved in dimethylformamide (300 ml), to the solution was added potassium carbonate (6.0 g) and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction solution and extraction with ethyl acetate was conducted. The solvent was distilled off under reduced pressure and the resulting crystals were recrystallized from ether to give 2-butyl-7-methoxycarbonyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine (10.3 g).

Workup

  1. customThe organic layer was separated
  2. distillationthe solvent was distilled off under reduced pressure
  3. dissolutionThe resulting residue was dissolved in dimethylformamide (300 ml), to the solution
  4. additionwas added potassium carbonate (6.0 g)
  5. stirringthe mixture was stirred at room temperature for 1 hour
  6. additionWater was added to the reaction solution and extraction with ethyl acetate
  7. distillationThe solvent was distilled off under reduced pressure
  8. customthe resulting crystals were recrystallized from ether

Sources & evidence

ORD record
ord-5e0192d32cc24e3e8c8abb93cd56ba12
Source dataset
uspto-grants-1997_01
Patent number
US05597820

Reaction notes

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