tert-Butyl methyl ether → 4-(tert-Butyl)-3,5-difluorophenol
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[C:6]([F:8])[CH:7]=1.CO[C:12]([CH3:15])([CH3:14])[CH3:13]>[Cl-].[Zr+4].[Cl-].[Cl-].[Cl-]>[C:12]([C:7]1[C:2]([F:1])=[CH:3][C:4]([OH:9])=[CH:5][C:6]=1[F:8])([CH3:15])([CH3:14])[CH3:13]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 55 °C
Procedure
A mixture of 3,5-difluorophenol (TCl, 14 g, 107 mmol), tert-butyl methyl ether (12.8 ml, 108 mmol) and zirconium(IV) chloride (25 g, 107 mmol) was stirred for 12 hours at 55 ° C., followed by addition of tert-butyl methyl ether (6.4 ml, 54 mmol). The additional injection of tert-butyl methyl ether (6.4 ml, 54 mmol), was repeated 8 times at intervals of 24 hours and then the reaction was quenched with saturated ammonium chloride aqueous solution and 2 M HCl aqueous solution. The whole was extracted with DCM, washed with brine, and dried over magnesium sulfate. The organic layer was evaporated to give a crude residue which was purified by silica gel column chromatography, eluting with gradually from hexane only to hexane/EtOAc (10:1), to give the title compound (10.8 g, 54%) as white solids.
Workup
- customat intervals of 24 hours
- customthe reaction was quenched with saturated ammonium chloride aqueous solution and 2 M HCl aqueous solution
- extractionThe whole was extracted with DCM
- washwashed with brine
- dry with materialdried over magnesium sulfate
- customThe organic layer was evaporated
- customto give a crude residue which
- customwas purified by silica gel column chromatography
- washeluting with gradually from hexane only to hexane/EtOAc (10:1)
Sources & evidence
- ORD record
- ord-3a7f23e3750f47fc8fdc1d1031370d93
- Source dataset
- uspto-grants-2009_11
- Patent number
- US07622589B2
Reaction notes
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