Chloroacetyl chloride → 6-acetyl-8-(tert-butyl)-3,4-dihydro-2H-1,4-benzoxazin-3-one

HRID 1296013Notes

Reaction equation

HRID 1296013 reaction equation
Cl[CH2:2][C:3](Cl)=[O:4].[NH2:6][C:7]1[CH:8]=[C:9]([C:18](=[O:20])[CH3:19])[CH:10]=[C:11]([C:14]([CH3:17])([CH3:16])[CH3:15])[C:12]=1[OH:13].C(=O)([O-])O.[Na+].C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.C(Cl)Cl>[C:18]([C:9]1[CH:10]=[C:11]([C:14]([CH3:16])([CH3:15])[CH3:17])[C:12]2[O:13][CH2:2][C:3](=[O:4])[NH:6][C:7]=2[CH:8]=1)(=[O:20])[CH3:19]

Participants

7

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 229299261-[3-Amino-5-(tert-butyl)-4-hydroxyphenyl]-1-ethanone

Product 1

HCID 229301966-acetyl-8-(tert-butyl)-3,4-dihydro-2H-1,4-benzoxazin-3-oneYield 28.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Chloroacetyl chloride (0.14 ml, 1.76 mmol) was added at room temperature to a solution of the 1-[3-amino-5-(tert-butyl)-4-hydroxyphenyl]-1-ethanone (300 mg, 1.45 mmol) in a methylene chloride (3 ml)-saturated aqueous sodium hydrogencarbonate (3 ml) mixed solvent, and the resultant mixture was stirred for 30 minutes. After adding ethyl acetate to the reaction mixture for separation, the organic layer was washed with brine. After drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was dissolved in dimethylformamide (6 ml), potassium carbonate (401 mg, 2.90 mmol) was added and the mixture was stirred at 70° C. for 7 hours under a nitrogen atmosphere. The solvent was distilled off under reduced pressure, and then ethyl acetate was added to the residue and the mixture was washed with water and brine in that order. After drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was subjected to silica gel chromatography (Wakogel-C200,7 g), and the fraction containing the target compound was obtained from the ethyl acetate-toluene (1:9˜1:6) fractions and crystallized from diethyl ether-diisopropyl ether to yield the title compound (102 mg, 28.5% yield) as yellow ochre crystals.

Workup

  1. additionmixed solvent
  2. customfor separation
  3. washthe organic layer was washed with brine
  4. dry with materialAfter drying over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. dissolutionThe residue was dissolved in dimethylformamide (6 ml)
  7. distillationThe solvent was distilled off under reduced pressure
  8. additionethyl acetate was added to the residue
  9. washthe mixture was washed with water and brine in that order
  10. dry with materialAfter drying over anhydrous magnesium sulfate
  11. distillationthe solvent was distilled off under reduced pressure
  12. additionthe fraction containing the target compound
  13. customwas obtained from the ethyl acetate-toluene (1:9˜1:6) fractions
  14. customcrystallized from diethyl ether-diisopropyl ether

Sources & evidence

ORD record
ord-2f7802a6712146ca832dac4388b4e102
Source dataset
uspto-grants-2007_07
Patent number
US07244730B2

Reaction notes

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