Diethyl Malonate → Ethyl 1-benzyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate

HRID 2269620

Reaction equation

HRID 2269620 reaction equation
[C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5]CC)=O.[H-].[Na+].[H][H].[CH2:16]([N:23]1[C:29](=O)[O:28]C(=O)[C:25]2=[CH:31][CH:32]=[CH:33][CH:34]=[C:24]12)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CN(C)C=O>[CH2:16]([N:23]1[C:24]2[C:25](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:3]([OH:5])=[C:2]([C:1]([O:9][CH2:10][CH3:11])=[O:8])[C:29]1=[O:28])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 520756N-Benzylisatoic anhydrideHCID 178418361HCID 178418361, compound

Product 1

HCID 54711837Ethyl 1-benzyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylateYield 68.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

In a solution of 4.50 g of diethyl malonate in 20 ml of N,N-dimethylformamide was gradually added 1.10 g of 62.4% sodium hydride at room temperature, and stirring was continued at room temperature until hydrogen evolution ceased. The reaction solution was heated to 80° C., and a solution of 6.70 g of N-benzylisatoic anhydride in 20 ml of N,N-dimethylformamide was added dropwise. After the addition, the reaction mixture was stirred under heating at 120° C. for 7 hours. After cooling to room temperature, the reaction mixture was poured into ice water and washed with ethyl acetate. The aqueous phase was made acidic with 1 N hydrochloric acid, and extracted with ethyl acetate. The organic phase was washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. After removal of the drying agent by filtration, the filtrate was concentrated under reduced pressure. The residue was crystallized from ethanol to give 5.88 g of ethyl 1-benzyl-4-hydroxy-1,2-dihydro-2-oxoquinoline-3-carboxylate.

Workup

  1. customat room temperature
  2. additionAfter the addition
  3. stirringthe reaction mixture was stirred
  4. temperatureunder heating at 120° C. for 7 hours
  5. temperatureAfter cooling to room temperature
  6. washwashed with ethyl acetate
  7. extractionextracted with ethyl acetate
  8. washThe organic phase was washed with a saturated aqueous sodium chloride solution
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customAfter removal of the drying agent
  11. filtrationby filtration
  12. concentrationthe filtrate was concentrated under reduced pressure
  13. customThe residue was crystallized from ethanol

Sources & evidence

ORD record
ord-7ea00b8b48ac4a6e87e7014f410351f6
Source dataset
uspto-grants-2001_12
Patent number
US06329525B1

Linked notes

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