tert-Butyl methyl ether → 4-(tert-Butyl)-3,5-difluorophenol

HRID 2108828Notes

Reaction equation

CO[C:3]([CH3:6])([CH3:5])[CH3:4].[F:7][C:8]1[CH:9]=[C:10]([OH:15])[CH:11]=[C:12]([F:14])[CH:13]=1>C(Cl)Cl.[Cl-].[Cl-].[Cl-].[Cl-].[Zr+4]>[C:3]([C:13]1[C:8]([F:7])=[CH:9][C:10]([OH:15])=[CH:11][C:12]=1[F:14])([CH3:6])([CH3:5])[CH3:4]

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of zirconium tetrachloride (1.17 g, 5 mmol) in DCM (10 ml) was added tert-butyl methyl ether (0.44 g, 5 mmol) at 0° C. After stirring for 30 minutes at 0° C., 3,5-difluorophenol (0.65 g, 5 mmol) in DCM was placed there and the mixture was stirred for 8 hours at 60° C. The reaction was quenched with saturated sodiumbicarbonate aqueous solution followed by addition of DCM. Then, organic layer was separated, dried over magnesium sulfate, evaporated in vacuo to give the residue which was purified through silica gel column chromatography eluting with hexane/EtOAc (20:1 to 4:1) to furnish 4-tert-butyl-3,5-difluorophenol as colorless oil (293 mg, 31%). 1H NMR (300 MHz, CDCl3): δ 1.42 (9H, t, J=2.2 Hz), 5.22 (1H, bs), 6.32 (2H, d, J=11.9 Hz).

Workup

stirringthe mixture was stirred for 8 hours at 60° C
customThe reaction was quenched with saturated sodiumbicarbonate aqueous solution
additionfollowed by addition of DCM
customThen, organic layer was separated
dry with materialdried over magnesium sulfate
customevaporated in vacuo
customto give the residue which
customwas purified through silica gel column chromatography
washeluting with hexane/EtOAc (20:1 to 4:1)

Sources & evidence

ORD record: ord-085dd2254c4043569fd29bb17517d02a
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07514457B2

Reaction notes

Loading…