Diethyl Malonate → 3-Quinolinecarboxylic acid, 1,2-dihydro-4-hydroxy-1-methyl-2-oxo-, ethyl ester

HRID 1513571Notes

Reaction equation

HRID 1513571 reaction equation
[C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5]CC)=O.[H-].[Na+].[CH3:14][N:15]1C(=O)O[C:18](=[O:19])[C:17]2=[CH:23][CH:24]=[CH:25][CH:26]=[C:16]12.C(OC(C)C)(C)C>CN(C=O)C>[OH:19][C:18]1[C:17]2[C:16](=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:15]([CH3:14])[C:3](=[O:5])[C:2]=1[C:1]([O:9][CH2:10][CH3:11])=[O:8]

Participants

6

Reactant 4

HCID 7761Diethyl MalonateHCID 7914Diisopropyl EtherHCID 24758Sodium hydrideHCID 25160N-Methylisatoic anhydride

Product 1

HCID 546829293-Quinolinecarboxylic acid, 1,2-dihydro-4-hydroxy-1-methyl-2-oxo-, ethyl esterYield 58.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of diethyl malonate (68.0 g, 0.425 mol) in DMF (400 mL) was added sodium hydride (66% in oil, 10.8 g, 0.30 mol) under ice-cooling, and the mixture was stirred at the same temperature for 5 min and at room temperature for 15 min. N-Methylisatoic anhydride (50.8 g, 0.287 mol) was added to the obtained mixture by small portions, and the mixture was stirred at 120° C. for 3 hr. Diisopropyl ether (500 mL) was added to the reaction mixture, and the precipitated solid was collected by filtration and washed with diisopropyl ether. The obtained solid was suspended in a mixture of methanol (250 mL) and water (500 mL), 5N hydrochloric acid (60 mL) was added dropwise, and the mixture was extracted twice with ethyl acetate. The combined organic layer was washed with water, and concentrated under reduced pressure. The residue was washed with diisopropyl ether to give the title compound (41.4 g, 58%).

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at 120° C. for 3 hr
  3. filtrationthe precipitated solid was collected by filtration
  4. washwashed with diisopropyl ether
  5. additionThe obtained solid was suspended in a mixture of methanol (250 mL) and water (500 mL), 5N hydrochloric acid (60 mL)
  6. additionwas added dropwise
  7. extractionthe mixture was extracted twice with ethyl acetate
  8. washThe combined organic layer was washed with water
  9. concentrationconcentrated under reduced pressure
  10. washThe residue was washed with diisopropyl ether

Sources & evidence

ORD record
ord-e01d69b910fb455fafb0b0235b29fbeb
Source dataset
uspto-grants-2012_07
Patent number
US08217176B2

Reaction notes

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