Ethyl Acetate → (S)-2-ethyl-7-methoxycarbonyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine

HRID 234906Notes

Reaction equation

HRID 234906 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+].Cl[C@H:25]([CH2:29][CH3:30])[C:26](Cl)=[O:27]>O>[CH2:29]([C@H: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)[CH3:30]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 7020619Benzoic acid, 4-amino-3-hydroxy-, methyl esterHCID 7568786(R)-2-chlorobutyryl chloride

Product 1

HCID 10633499(S)-2-ethyl-7-methoxycarbonyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazineYield 88.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 2-amino-5-methoxycarbonylphenol [Tetrahedron, 46(15), 5177-5186 (1990)] (7.50 g) in a mixed solvent of ethyl acetate (60 ml) and water (60 ml) were added sodium hydrogen carbonate (5.20 g) and (R)-2-chlorobutyryl chloride (7.50 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 (90 ml), to the solution was added potassium carbonate (6.20 g) and the mixture was stirred at room temperature overnight. Water was added to the reaction solution and the resulting crystals were taken by filtration to give (S)-2-ethyl-7-methoxycarbonyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine (9.38 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 (90 ml), to the solution
  4. additionwas added potassium carbonate (6.20 g)
  5. stirringthe mixture was stirred at room temperature overnight
  6. additionWater was added to the reaction solution
  7. filtrationthe resulting crystals were taken by filtration

Sources & evidence

ORD record
ord-b7323edc52714161a112813d18b22f56
Source dataset
uspto-grants-1997_01
Patent number
US05597820

Reaction notes

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