Pentane → 1-Cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic Acid Ethyl Ester

HRID 620870Notes

Reaction equation

HRID 620870 reaction equation
F[C:2]1[C:20]([F:21])=[C:19]([F:22])[C:18]([F:23])=[CH:17][C:3]=1[C:4]([C:6](=[CH:12][NH:13][CH:14]1[CH2:16][CH2:15]1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])=[O:5].[H-].[Na+].CCCCC.[H][H]>O1CCOCC1.O1CCCC1>[CH:14]1([N:13]2[C:17]3[C:3](=[CH:2][C:20]([F:21])=[C:19]([F:22])[C:18]=3[F:23])[C:4](=[O:5])[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:12]2)[CH2:16][CH2:15]1

Participants

7

Reactant 4

HCID 8003PentaneHCID 24758Sodium hydride2×HCID 178418361HCID 178418361, compoundHCID 178471877HCID 178471877, compound

Product 1

HCID 5354151-Cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic Acid Ethyl EsterYield 50.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

To 2.0 g (6.0 mmol) of the 2-(2,3,4,5-tetra- fluorobenzoyl)-3-cyclopropylaminoacrylic acid, ethyl ester in 60 ml of dry dioxane was added 0.29 g of sodium hydride 50% dispersion) that was prewashed with pentane. The sodium hydride was delivered in 10 ml of dry tetrahydrofuran at 0° C. When evolution of hydrogen began to slow, the mixture was refluxed for two hours. It was concentrated, and the residue taken up in dichloromethane, which was water extracted, dried (MgSO4), and concentrated. The residue was purified by column chromatography (silica gel 70-200 mesh, using chloroform:hexane:isopropanol, 4:5:1) to give 0.95 g of the 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, ethyl ester, mp 168°-169° C. This material was dissolved in acetic acid at 100° C. and was treated with 10 ml of 0.5 N hydrochloric acid for 2.5 hours. The mixture was cooled and water added. The solids were then collected to give 0.7 g of 1-cyclopropyl-1,4-dihydro-4-oxo-6,7,8-trifluoro-3-quinolinecarboxylic acid, mp 226°-228° C. By the same methods 5-amine-7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid can be prepared.

Workup

  1. temperaturethe mixture was refluxed for two hours
  2. concentrationIt was concentrated
  3. extractionextracted
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (silica gel 70-200 mesh, using chloroform:hexane:isopropanol, 4:5:1)

Sources & evidence

ORD record
ord-951511b68e12415fa004ff08a6cca7c7
Source dataset
uspto-grants-1989_04
Patent number
US04822801

Reaction notes

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