Ethyl Acetate → Methyl 6-bromo-2,2-dimethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-5-carboxylate

HRID 1182760Notes

Reaction equation

HRID 1182760 reaction equation
[Br:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([N+:12]([O-])=O)[C:5]([NH:15][CH:16]([CH2:18]C(OCC)=O)[CH3:17])=[CH:4][CH:3]=1.[Sn](Cl)Cl.[C:27](OCC)(=[O:29])C.C(=O)([O-])O.[Na+]>C(O)C>[Br:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]2[C:5]([NH:15][C:16]([CH3:17])([CH3:18])[C:27](=[O:29])[NH:12]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24479Stannous ChlorideHCID 516892Sodium BicarbonateHCID 67210813Methyl 6-bromo-3-[(2-ethoxycarbonyl)propan-2-yl]amino-2-nitrobenzoate

Product 1

HCID 24780709Methyl 6-bromo-2,2-dimethyl-3-oxo-1,2,3,4-tetrahydroquinoxaline-5-carboxylateYield 70%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Methyl 6-bromo-3-[(2-ethoxycarbonyl)propan-2-yl]amino-2-nitrobenzoate (Reference Compound No. 1-(5), 105 mg, 0.26 mmol) was dissolved in anhydrous ethanol (4.5 mL), tin (II) chloride (247 mg, 1.30 mmol) was added thereto, and then the reaction mixture was refluxed for 5 hours. After cooling down, ethyl acetate (25 mL) was added to the reaction mixture, the mixture was neutralized with aqueous sodium hydrogen carbonate solution, and then filtered on celite. After the filtrate was partitioned, the water layer was extracted with ethyl acetate (10 mL, twice), the combined organic layer was washed with water (50 mL, twice) and saturated brine (50 mL) successively, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give the titled reference compound (56.3 mg) as a pale yellow solid. (Yield 70%)

Workup

  1. temperaturethe reaction mixture was refluxed for 5 hours
  2. temperatureAfter cooling down
  3. filtrationfiltered on celite
  4. customAfter the filtrate was partitioned
  5. extractionthe water layer was extracted with ethyl acetate (10 mL
  6. washtwice), the combined organic layer was washed with water (50 mL
  7. dry with materialtwice) and saturated brine (50 mL) successively, dried over anhydrous magnesium sulfate
  8. customthe solvent was removed under reduced pressure
  9. customThe obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-c6e625755d8d4416abe122c019e2a5cb
Source dataset
uspto-grants-2014_03
Patent number
US08664221B2

Reaction notes

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