Citric Acid → HCID 86641942, compound

HRID 384118Notes

Reaction equation

HRID 384118 reaction equation
CO[C:3]([C:5]1[C:10](F)=[CH:9][CH:8]=[C:7]([Cl:12])[N:6]=1)=[O:4].[C:13]1([OH:19])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+].Cl.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O.C1(C)C=CC=CC=1.[H-].C([Al+]CC(C)C)C(C)C.O>[Cl:12][C:7]1[N:6]=[C:5]([CH2:3][OH:4])[C:10]([O:19][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:9][CH:8]=1

Participants

10

Reactant 5

HCID 311Citric AcidHCID 313Hydrochloric AcidHCID 996PhenolHCID 11430Potassium CarbonateHCID 46311240HCID 46311240, compound

Product 1

HCID 86641942HCID 86641942, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 21225700DiisobutylaluminumhydrideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 6-chloro-3-fluoropyridin-2-carboxylic acid methyl ester (245 mg) in dimethylformamide (3 ml), 200 mg of phenol and 393 mg of potassium carbonate were added, and the reaction solution was stirred at 100° C. for 1.5 hours. The reaction solution was cooled, then 1N hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with a saturated saline solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to afford a crude product as a brown oil. To a solution of the crude product in toluene (5 ml), 9.9 ml of diisobutylaluminum hydride (1.0M hexane solution) was added at −78° C., and the reaction solution was stirred for 2 hours while increasing the temperature of the reaction solution to room temperature. To the reaction solution were added water and 10% aqueous citric acid sequentially, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with a saturated saline solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue obtained was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (98:2-50:50)) to afford the title compound as a pale yellow oil.

Workup

  1. temperatureThe reaction solution was cooled
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe combined organic layers were washed with a saturated saline solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customto afford a crude product as a brown oil
  7. stirringthe reaction solution was stirred for 2 hours
  8. temperaturewhile increasing the temperature of the reaction solution to room temperature
  9. extractionthe mixture was extracted with ethyl acetate
  10. washThe combined organic layers were washed with a saturated saline solution
  11. dry with materialdried over anhydrous sodium sulfate
  12. distillationThe solvent was distilled off under reduced pressure
  13. customthe residue obtained
  14. customwas purified by silica gel column chromatography (eluent: hexane/ethyl acetate (98:2-50:50))

Sources & evidence

ORD record
ord-14d89ee2882e4809af2adf771bbc64fd
Source dataset
uspto-grants-2013_02
Patent number
US08367708B2

Reaction notes

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