Diethyl (ethoxymethylene)malonate → Ethyl 4-hydroxy-7-methoxyquinoline-3-carboxylate

HRID 454184Notes

Reaction equation

HRID 454184 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([NH2:9])[CH:4]=1.C([O:12][CH:13]=[C:14]([C:20](OCC)=O)[C:15]([O:17][CH2:18][CH3:19])=[O:16])C.C(C1C=NC2C(C=1)=CC=C(OC1C3C(=CC(OCC4CCN(C)CC4)=C(OC)C=3)N=CN=1)C=2)#N>C1(OC2C=CC=CC=2)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:6]([C:13](=[O:12])[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:20][NH:9]2)=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 6871Diethyl (ethoxymethylene)malonateHCID 108243-MethoxyanilineHCID 220305324-(3-Cyanoquinolin-7-yloxy)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazoline

Product 1

HCID 296364Ethyl 4-hydroxy-7-methoxyquinoline-3-carboxylateYield 45%

Reagents, catalysts & solvents 1

HCID 7583Diphenyl EtherSolvent

Conditions

Temperature
240 °C

Procedure

m-Anisidine (50 g, 407 mmol) and diethyl ethoxymethylenemalonate (102 g, 407 mmol) were heated at 60° C. for 20 minutes. Diphenyl ether (270 ml) was then added and the temperature was raised to 240° C. over 30 minutes. The ethanol formed distilled off. Heating was maintained at this temperature for 1 hour then the reaction mixture was allowed to cool to 120° C. at which point the reaction mixture was diluted with heptane and allowed to stand overnight at ambient temperature. The brown solid was collected by filtration and washed with methanol and ether to give ethyl 7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate (45 g, 45%). This reaction was repeated twice.

Workup

  1. distillationdistilled off
  2. temperatureHeating
  3. temperaturewas maintained at this temperature for 1 hour
  4. temperatureto cool to 120° C. at which
  5. additionwas diluted with heptane
  6. filtrationThe brown solid was collected by filtration
  7. washwashed with methanol and ether

Sources & evidence

ORD record
ord-48122447182f416f976410885abcdf8e
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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