Sodium hydride → Ethyl 6,7,8-trifluoro-1-(4-thiazolylmethyl)-1,4-dihydro-4-oxoquinoline-3-carboxylate

HRID 440268Notes

Reaction equation

HRID 440268 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:13])[C:11]=1[F:12])[N:8]=[CH:7][C:6]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:5]2[OH:19].[H-].[Na+].Cl.Cl[CH2:24][C:25]1[N:26]=[CH:27][S:28][CH:29]=1>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:13])[C:11]=1[F:12])[N:8]([CH2:24][C:25]1[N:26]=[CH:27][S:28][CH:29]=1)[CH:7]=[C:6]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:5]2=[O:19]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27339723-Quinolinecarboxylic acid, 1,4-dihydro-4-oxo-6,7,8-trifluoro-, ethyl esterHCID 27632894-(Chloromethyl)-1,3-thiazole hydrochloride

Product 1

HCID 54420378Ethyl 6,7,8-trifluoro-1-(4-thiazolylmethyl)-1,4-dihydro-4-oxoquinoline-3-carboxylateYield 22.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

1.5 g of ethyl 6,7,8-trifluoro-4-hydroxyquinoline-3-carboxylate was dissolved in 30 ml of DMF, and 0.43 g of 60% oily sodium hydride was added, followed by stirring at 80° C. in a nitrogen gas stream for 20 minutes. To this solution, 1.9 g of 4-chloromethylthiazole hydrochloride was added, followed by stirring at constant temperature for 15 hours, after which the reaction mixture was concentrated to dryness. The residue was dissolved in CHCl3 ; the organic layer was washed with water and dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate=1:2) to yield 0.46 g of ethyl 6,7,8-trifluoro-1-(4-thiazolylmethyl)-1,4-dihydro-4-oxoquinoline-3-carboxylate as a colorless powder. This product was suspended in a mixture of acetic acid and water (3 ml:3 ml); 0.33 ml of sulfuric acid was added, followed by stirring at 120° C. for 30 minutes. The reaction mixture was allowed to cool to room temperature, and the resulting crystal was collected by filtration to yield 0.38 g of the title compound as a colorless powder.

Workup

  1. stirringby stirring at constant temperature for 15 hours
  2. concentrationafter which the reaction mixture was concentrated to dryness
  3. dissolutionThe residue was dissolved in CHCl3
  4. washthe organic layer was washed with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane-ethyl acetate=1:2)

Sources & evidence

ORD record
ord-180c3642dfbf4f34bc895bf9a1e9cc55
Source dataset
uspto-grants-1996_05
Patent number
US05519024

Reaction notes

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