Sodium → Ethyl 1-ethyl-5,6-dimethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 525958Notes

Reaction equation

HRID 525958 reaction equation
[CH2:1]([N:3]1[C:8]2[CH:9]=[CH:10][C:11]([O:15][CH3:16])=[C:12]([O:13][CH3:14])[C:7]=2C(=O)O[C:4]1=O)[CH3:2].[CH2:19]([O:21][C:22](=[O:26])/[CH:23]=[CH:24]\[O-:25])[CH3:20].[Na]>CN(C)C=O>[CH2:1]([N:3]1[C:8]2[C:7](=[C:12]([O:13][CH3:14])[C:11]([O:15][CH3:16])=[CH:10][CH:9]=2)[C:24](=[O:25])[C:23]([C:22]([O:21][CH2:19][CH3:20])=[O:26])=[CH:4]1)[CH3:2]

Participants

5

Reactant 3

HCID 5360545SodiumHCID 867328231-ethyl-5,6-dimethoxy-1H-benzo[d][1,3]oxazine-2,4-dioneHCID 86732825(Z)-3-ethoxy-3-oxoprop-1-en-1-olate

Product 1

HCID 86732824Ethyl 1-ethyl-5,6-dimethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylateYield 33.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Under N2, 1-ethyl-5,6-dimethoxy-1H-benzo[d][1,3]oxazine-2,4-dione (12 g, 43.5 mmol) in N,N-Dimethylformamide (DMF) (250 mL) was added to a solution of (Z)-3-ethoxy-3-oxoprop-1-en-1-olate, Sodium salt (18.01 g, 130 mmol) in N,N-Dimethylformamide (DMF) (150 mL) with stirring. The resulting solution was stirred at 110° C. for 3 h. After cooling down, the mixture was concentrated in vacuo and the orange residue was taken up in water. The aqueous solution was washed with ethyl ether (3×), acidified to pH˜2 with 6 N HCl, and extracted with DCM (4×). The organic extracts were dried over Na2SO4, filtered and concentrated. The residue was purified by normal phase silica gel chromatography (CombiFlash), eluting with MeOH/DCM (0-15%) to afford ethyl 1-ethyl-5,6-dimethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate (4.5 g, 14.74 mmol, 33.9% yield) as a brown oil that turned into a brown solid after overnight. LCMS: (M+H)+: 306.4.

Workup

  1. stirringThe resulting solution was stirred at 110° C. for 3 h
  2. temperatureAfter cooling down
  3. concentrationthe mixture was concentrated in vacuo
  4. washThe aqueous solution was washed with ethyl ether (3×)
  5. extractionextracted with DCM (4×)
  6. dry with materialThe organic extracts were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by normal phase silica gel chromatography (CombiFlash)
  10. washeluting with MeOH/DCM (0-15%)

Sources & evidence

ORD record
ord-67ed1d5c32ca43eabcea7efd539ba8a0
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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