Water → 6-(2,6-Difluorophenyl)-5-fluoropicolinic acid

HRID 705233

Reaction equation

HRID 705233 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[C:14]([F:15])=[CH:13][CH:12]=[C:11]([CH3:16])[N:10]=1.[O-:17][Mn](=O)(=O)=O.[K+].[OH2:23]>>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[N:10]=[C:11]([C:16]([OH:17])=[O:23])[CH:12]=[CH:13][C:14]=1[F:15]

Participants

4

Reactant 3

HCID 962WaterHCID 516875Potassium Permanganate2×HCID 592265082-(2,6-Difluorophenyl)-3-fluoro-6-methylpyridine

Product 1

HCID 592265526-(2,6-Difluorophenyl)-5-fluoropicolinic acidYield 32%

Procedure

To a solution of 2-(2,6-difluorophenyl)-3-fluoro-6-methylpyridine (1.0 equiv.) in water (0.05 M) was added KMnO4 (2.0 equiv.) and the reaction was heated to reflux overnight. Another 2.0 equiv. of KMnO4 were added and stirred at reflux for another 8 hours. The solution was cooled to room temperature, filtered through Celite and washed with water. The filtrate was acidified with 6N HCl to pH=3, the white precipitate was filtered. The filtrate was further acidified to pH=1 and filtered again. The filtrate was extracted with ethyl acetate until no more product was in the aqueous layer. The organic phase was washed with brine and dried over magnesium sulfate, filtered, and concentrated. The residue was dissolved in ethyl acetate, washed with 1N NaOH, the aqueous layer was acidified to pH=1 and the white crystals were filtered. The combined products yielded 6-(2,6-difluorophenyl)-5-fluoropicolinic acid in 32% yield as a white solid. LC/MS=254.0 (M+H), Rt=0.71 min.

Workup

  1. temperaturethe reaction was heated
  2. temperatureto reflux overnight
  3. temperatureat reflux for another 8 hours
  4. filtrationfiltered through Celite
  5. washwashed with water
  6. filtrationthe white precipitate was filtered
  7. filtrationfiltered again
  8. extractionThe filtrate was extracted with ethyl acetate until no more product
  9. washThe organic phase was washed with brine
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. dissolutionThe residue was dissolved in ethyl acetate
  14. washwashed with 1N NaOH
  15. filtrationthe white crystals were filtered

Sources & evidence

ORD record
ord-c3cd355230064c87b3dea43d781afd9d
Source dataset
uspto-grants-2015_11
Patent number
US09173883B2

Linked notes

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