Potassium Hydroxide → Fluoroquinolonic acid

HRID 1284498Notes

Reaction equation

HRID 1284498 reaction equation
[H-].[Na+].Cl[C:4]1[CH:22]=[C:21]([Cl:23])[C:20]([F:24])=[CH:19][C:5]=1[C:6]([C:8](=[CH:14][NH:15][CH:16]1[CH2:18][CH2:17]1)[C:9]([O:11]CC)=[O:10])=[O:7].[OH-].[K+]>O1CCOCC1.O>[Cl:23][C:21]1[CH:22]=[C:4]2[C:5]([C:6](=[O:7])[C:8]([C:9]([OH:11])=[O:10])=[CH:14][N:15]2[CH:16]2[CH2:18][CH2:17]2)=[CH:19][C:20]=1[F:24]

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 178471868HCID 178471868, compound

Product 1

HCID 483180Fluoroquinolonic acidYield 106.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Procedure

3.44 g of 80 percent strength sodium hydride are added in portions to a solution of 31.9 g of ethyl 2-(2,4-dichloro-5-fluoro-benzoyl)-3-cyclopropylaminoacrylate in 300 ml of anhydrous dioxane, while cooling with ice and stirring. The mixture is then stirred at room temperature for 30 minutes and under reflux for 2 hours and the dioxane is stripped off in vacuo. The residue (40.3 g) is suspended in 150 ml of water, 6.65 g of potassium hydroxide are added and the mixture is refluxed for 1.5 hours. The warm solution is filtered and the residue is rinsed with water. The filtrate is then acidified to pH 1-2 with half-concentrated hydrochloric acid, while cooling with ice, and the precipitate is filtered off with suction, washed with water and dried in vacuo at 100° C. 27.7 g of 7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid of melting point 234°-237° C. are obtained in this manner.

Workup

  1. temperaturewhile cooling with ice
  2. stirringThe mixture is then stirred at room temperature for 30 minutes
  3. temperatureunder reflux for 2 hours
  4. temperaturethe mixture is refluxed for 1.5 hours
  5. filtrationThe warm solution is filtered
  6. washthe residue is rinsed with water
  7. temperaturewhile cooling with ice
  8. filtrationthe precipitate is filtered off with suction
  9. washwashed with water
  10. customdried in vacuo at 100° C

Sources & evidence

ORD record
ord-19646b76c11d492b90184edf2a5554f1
Source dataset
uspto-grants-1986_01
Patent number
US04563459

Reaction notes

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