Triethyl Phosphate → Ethyl 1-ethyl-5-fluoro-6,7-dimethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate
Reaction equation
[F:1][C:2]1[C:11]([O:12][CH3:13])=[C:10]([O:14][CH3:15])[CH:9]=[C:8]2[C:3]=1[C:4](=[O:21])[C:5]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:6][NH:7]2.F[C:23]1C=C2C(C(=O)C(C(OCC)=O)=CN2)=C(OC)[C:24]=1OC.C(=O)([O-])[O-].[K+].[K+].P(OCC)(OCC)(OCC)=O>O>[CH2:23]([N:7]1[C:8]2[C:3](=[C:2]([F:1])[C:11]([O:12][CH3:13])=[C:10]([O:14][CH3:15])[CH:9]=2)[C:4](=[O:21])[C:5]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:6]1)[CH3:24]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 120 °C
Procedure
A mixture of ethyl 5-fluoro-6,7-dimethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate and ethyl 7-fluoro-5,6-dimethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate (103 g, 349 mmol), and potassium carbonate (72.3 g, 523 mmol) in triethyl phosphate (297 ml, 1744 mmol) was stirred at 120° C. for 8 h. LCMS indicated completion of the reaction. The reaction mixture was cooled down to rt and diluted with water, extracted with DCM, dried over sodium sulfate and concentrated in vacuo. The crude material was recrystallized in EtOH, the precipitate was collected by filtration and washed by cold EtOH and dried in air. Another recrystallization afforded pure ethyl 1-ethyl-5-fluoro-6,7-dimethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate (65 g, 201 mmol, 57.6% yield) as a brown solid. LCMS: (M+H)+: 324.1.
Workup
- customcompletion of the reaction
- temperatureThe reaction mixture was cooled down to rt
- extractionextracted with DCM
- dry with materialdried over sodium sulfate
- concentrationconcentrated in vacuo
- customThe crude material was recrystallized in EtOH
- filtrationthe precipitate was collected by filtration
- washwashed by cold EtOH
- customdried in air
- customAnother recrystallization
Sources & evidence
- ORD record
- ord-a0e1ef3c75644de480d9b9e5db872a98
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09340556B2
Reaction notes
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