Diethyl (ethoxymethylene)malonate → ETHYL 7-FLUORO-4-HYDROXY-6-METHOXYQUINOLINE-3-CARBOXYLATE
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][CH3:10])[NH2:5].CC[O:13][CH:14]=[C:15]([C:21](OCC)=O)[C:16]([O:18][CH2:19][CH3:20])=[O:17]>CCCCCC>[F:1][C:2]1[CH:3]=[C:4]2[C:6]([C:14](=[O:13])[C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:21][NH:5]2)=[CH:7][C:8]=1[O:9][CH3:10]Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 110 °C
Procedure
A mixture of 3-fluoro-4-methoxyaniline (3.00 g, 21.26 mmol) and diethyl ethoxymethylene malonate (4.59 g, 21.26 mmol) is heated at 110° C. for 1 hour then cooled to room temperature. Hexane is added and the solids collected by filtration. This material is suspended in 45 mL of a 3:1 mixture of diphenyl ether:biphenyl and the mixture is heated at reflux for 2 hours to provide a brown solution. The reaction mixture is cooled to room temperature and hexane is added. The resultant solid is collected by filtration washing with hexane to provide 2.62 g of ethyl 7-fluoro-6-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylate as a white solid, mp>300° C.
Workup
- temperaturethen cooled to room temperature
- filtrationthe solids collected by filtration
- additionThis material is suspended in 45 mL of a 3:1 mixture of diphenyl ether
- temperaturebiphenyl and the mixture is heated
- temperatureat reflux for 2 hours
- customto provide a brown solution
- temperatureThe reaction mixture is cooled to room temperature
- filtrationThe resultant solid is collected by filtration
- washwashing with hexane
Sources & evidence
- ORD record
- ord-5248a094edc746ebaac75832ae0757d5
- Source dataset
- uspto-grants-2004_08
- Patent number
- US06780996B2
Reaction notes
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