Hydrochloric Acid → HCID 90384419, compound

HRID 928655Notes

Reaction equation

HRID 928655 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH2:7](Br)[C:8]#[CH:9].[Br:11][C:12]1[CH:17]=[C:16]([F:18])[C:15]([F:19])=[CH:14][C:13]=1[OH:20].[F-].[Cs+].CN(C)C1C=CC=CC=1.Cl>CN(C=O)C.C(OCC)(=O)C>[Br:11][C:12]1[C:13]2[O:20][C:8]([CH3:9])=[CH:7][C:14]=2[C:15]([F:19])=[C:16]([F:18])[CH:17]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 949N,N-DimethylanilineHCID 7842Propargyl bromideHCID 11430Potassium CarbonateHCID 25953Cesium fluorideHCID 27362882-Bromo-4,5-difluorophenol

Product 1

HCID 90384419HCID 90384419, compoundYield 14%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Potassium carbonate (1.38 g, 10.0 mmol) and propargyl bromide (0.414 mL, 5.50 mmol) were added to a solution (25 mL) of 2-bromo-4,5-difluorophenol (1.05 g, 5.00 mmol) in DMF, and stirred at room temperature overnight. The solvent was distilled away under reduced pressure, and after diluted with ethyl acetate, the resultant was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled away, and the residue was purified by silica gel chromatography (hexane/ethyl acetate). To the resulting compound (1.18 g, 4.78 mmol), cesium fluoride (872 mg, 5.74 mmol) and dimethylaniline (7 mL) were added, and stirred at 170° C. overnight. To the reaction solution, ethyl acetate and a 2 N hydrochloric acid aqueous solution were added and stirred. After the insoluble material was filtered off, extraction was performed with ethyl acetate. The organic phase was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane) to thus obtain the title compound.

Workup

  1. distillationThe solvent was distilled away under reduced pressure
  2. additionafter diluted with ethyl acetate
  3. washthe resultant was washed with water and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationThe solvent was distilled away
  6. customthe residue was purified by silica gel chromatography (hexane/ethyl acetate)
  7. stirringstirred at 170° C. overnight
  8. stirringstirred
  9. filtrationAfter the insoluble material was filtered off
  10. extractionextraction
  11. washThe organic phase was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. distillationThe solvent was distilled away under reduced pressure
  14. customThe resulting residue was purified by silica gel chromatography (hexane)

Sources & evidence

ORD record
ord-4eefd856b4c244ad9e768b9b0ecf1614
Source dataset
uspto-grants-2016_03
Patent number
US09290487B2

Reaction notes

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