Potassium Acetate → 4-Chloro-2-(difluoromethoxy)phenol

HRID 2178126Notes

Reaction equation

HRID 2178126 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[C:4]([O:9][CH:10]([F:12])[F:11])[CH:3]=1.C([O-])(=[O:15])C.[K+].OOS([O-])=O.[K+]>C1COCC1.CCOC(C)=O.O.C(OCC)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:15])=[C:4]([O:9][CH:10]([F:12])[F:11])[CH:3]=1

Participants

9

Reactant 3

HCID 517044Potassium AcetateHCID 222953811-Bromo-4-chloro-2-(difluoromethoxy)benzeneHCID 23707502Potassium hydroxy sulfite

Product 1

HCID 600510324-Chloro-2-(difluoromethoxy)phenol

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent3×HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-chloro-2-(difluoromethoxy)bromobenzene (Preparation 27, 200 mg, 0.63 mmol) in THF (6 mL) was added bis-neopentylglycolatodiboron (149 mg, 0.660 mmol), potassium acetate (191 mg, 1.88 mmol) and Pd(dppf)Cl2 (23 mg, 0.031 mmol). The reaction mixture was heated to reflux for 4 hours before cooling and diluting with EtOAc and water. The organic layer was collected, washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in acetone (6 mL) and treated with a solution of oxone (1.64 g, 2.54 mmol) in water (6 mL). The reaction mixture was stirred at room temperature for 15 minutes. The reaction mixture was diluted with diethyl ether (10 mL) and water (5 mL). The organic layer was collected, washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 0-15% diethyl ether in DCM to afford the title compound.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 4 hours
  3. temperaturebefore cooling
  4. customThe organic layer was collected
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved in acetone (6 mL)
  9. customThe organic layer was collected
  10. washwashed with brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified
  14. washeluting with 0-15% diethyl ether in DCM

Sources & evidence

ORD record
ord-3e0d3f3b75c640f580e90c4fb4df631f
Source dataset
uspto-grants-2015_06
Patent number
US09067922B2

Reaction notes

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