Water → 1-(Benzyloxy)-4-(difluoromethoxy)benzene

HRID 1420854Notes

Reaction equation

HRID 1420854 reaction equation
Cl[C:2]([F:9])([F:8])C(OCC)=O.[CH2:10]([O:17][C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH2:10]([O:17][C:18]1[CH:19]=[CH:20][C:21]([O:24][CH:2]([F:9])[F:8])=[CH:22][CH:23]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7638MonobenzoneHCID 11430Potassium Carbonate3×HCID 67843Acetic acid, 2-chloro-2,2-difluoro-, ethyl ester3×

Product 1

HCID 132534121-(Benzyloxy)-4-(difluoromethoxy)benzeneYield 27%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Ethyl chlorodifluoroacetate (25 mL, 0.20 mol) was added to 4-(benzyloxy)phenol (20.10 g, 0.10 mol), and potassium carbonate (41.90 g, 0.30 mol) in dimethylformamide (200 mL) and the mixture was stirred at 80° C. for 18 h. Additional ethyl chlorodifluoroacetate (12.7 mL, 0.10 mol) and potassium carbonate (27.74 g, 0.20 mol) were added and the mixture was stirred at 80° C. for 6 h. Additional ethyl chlorodifluoroacetate (12.7 mL, 0.10 mol) and potassium carbonate (27.74 g, 0.20 mol) were added and the mixture was stirred at 120° C. for 15 h. The mixture was cooled, poured into water (1000 mL) and extracted with ethyl acetate (500 mL). The organic fraction was washed with aqueous sodium hydroxide (1M, 500 mL) and brine (500 mL), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with hexane/CH2Cl2 (90:10) to give the title compound as a colorless solid (6.67 g, 27%). 1H NMR (360 MHz, CDCl3) δ 5.05 (2H, s), 6.42 (1H, t, J 74 Hz), 6.94 (2H, m) 7.06 (2H, m), and 7.31-7.44 (5H, m).

Workup

  1. stirringthe mixture was stirred at 80° C. for 6 h
  2. stirringthe mixture was stirred at 120° C. for 15 h
  3. temperatureThe mixture was cooled
  4. extractionextracted with ethyl acetate (500 mL)
  5. washThe organic fraction was washed with aqueous sodium hydroxide (1M, 500 mL) and brine (500 mL)
  6. dry with materialdried (MgSO4)
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel
  9. washeluting with hexane/CH2Cl2 (90:10)

Sources & evidence

ORD record
ord-13570fa63158494d87cc819e7bfa0347
Source dataset
uspto-grants-2000_06
Patent number
US06071927

Reaction notes

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