Triethyl Phosphate → Ethyl 1-ethyl-8-fluoro-6,7-dimethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 525889Notes

Reaction equation

[F:1][C:2]1[C:3]([O:20][CH3:21])=[C:4]([O:18][CH3:19])[CH:5]=[C:6]2[C:11]=1[NH:10][CH:9]=[C:8]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:7]2=[O:17].C(=O)([O-])[O-].[K+].[K+].P(OCC)(OCC)(O[CH2:31][CH3:32])=O>O>[CH2:31]([N:10]1[C:11]2[C:6](=[CH:5][C:4]([O:18][CH3:19])=[C:3]([O:20][CH3:21])[C:2]=2[F:1])[C:7](=[O:17])[C:8]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:9]1)[CH3:32]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of ethyl 8-fluoro-6,7-dimethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate (41 g, 139 mmol) and potassium carbonate (28.8 g, 208 mmol) in triethyl phosphate (118 ml, 694 mmol) was stirred at 120° C. for 5 h. LCMS indicated completion of the reaction. Then the reaction mixture was cooled down and diluted with water, extracted with DCM, dried over sodium sulfate and evaporated in vacuo. The crude material was purified by reverse phase automatic C-18 column chromatography (Combiflash RF, 130 g column), eluting with Acetonitrile/Water (10-80%) to afford ethyl 1-ethyl-8-fluoro-6,7-dimethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate (26 g, 80 mmol, 57.9% yield) as a white solid.

Workup

customcompletion of the reaction
temperatureThen the reaction mixture was cooled down
extractionextracted with DCM
dry with materialdried over sodium sulfate
customevaporated in vacuo
customThe crude material was purified by reverse phase automatic C-18 column chromatography (Combiflash RF, 130 g column)
washeluting with Acetonitrile/Water (10-80%)

Sources & evidence

ORD record: ord-7de7bb11a00e4b05b59380038dbb7c14
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09340556B2

Reaction notes

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