Hydrochloric Acid → HCID 86641947, compound

HRID 384141Notes

Reaction equation

HRID 384141 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]#N)[CH:5]=[CH:4][N:3]=1.[C:10]1([OH:16])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(=O)([O-])[O-:18].[K+].[K+].Cl>CN(C)C=O.C1(C)C=CC=CC=1.[H-].C([Al+]CC(C)C)C(C)C.O>[O:16]([C:2]1[CH:7]=[C:6]([CH:5]=[CH:4][N:3]=1)[CH:8]=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 996PhenolHCID 11430Potassium CarbonateHCID 5686382-Chloro-4-cyanopyridine

Product 1

HCID 86641947HCID 86641947, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 21225700DiisobutylaluminumhydrideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2-chloro-4-cyanopyridine (1.5 g) in dimethylformamide (10 ml), 1.52 g of phenol and 2.2 g of potassium carbonate were added, and the reaction solution was stirred overnight at 120° C. 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 then 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), chloroform/methanol (99.5:0.5-92:8)) to afford a crude product as a white solid. To a solution of the crude product in toluene (10 ml), 15 ml of diisobutylaluminum hydride (1.0M toluene solution) was added at −78° C., and the reaction solution was stirred at the same temperature for 2 hours. To the reaction solution were added water and a saturated aqueous ammonium chloride solution sequentially, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with a saturated saline solution and then 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 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. customthe residue obtained
  7. customwas purified by silica gel column chromatography (eluent: hexane/ethyl acetate (98:2-50/50), chloroform/methanol (99.5:0.5-92:8))
  8. customto afford a crude product as a white solid
  9. stirringthe reaction solution was stirred at the same temperature for 2 hours
  10. extractiona saturated aqueous ammonium chloride solution sequentially, and the mixture was extracted with ethyl acetate
  11. washThe combined organic layers were washed with a saturated saline solution
  12. dry with materialdried over anhydrous sodium sulfate
  13. distillationThe solvent was distilled off under reduced pressure
  14. customthe residue obtained
  15. customwas purified by silica gel column chromatography (eluent: hexane/ethyl acetate (98:2-50/50))

Sources & evidence

ORD record
ord-47b9a16ed06a467e82eda120128e5fe3
Source dataset
uspto-grants-2013_02
Patent number
US08367708B2

Reaction notes

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