Sodium hydride → Tert-butyl(4-tert-butyl-3,5-difluorophenoxy)acetate

HRID 2108829Notes

Reaction equation

HRID 2108829 reaction equation
[H-].[Na+].[C:3]([C:7]1[C:12]([F:13])=[CH:11][C:10]([OH:14])=[CH:9][C:8]=1[F:15])([CH3:6])([CH3:5])[CH3:4].Br[CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]>C1COCC1>[C:21]([O:20][C:18](=[O:19])[CH2:17][O:14][C:10]1[CH:9]=[C:8]([F:15])[C:7]([C:3]([CH3:6])([CH3:4])[CH3:5])=[C:12]([F:13])[CH:11]=1)([CH3:24])([CH3:23])[CH3:22]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 670464324-(tert-Butyl)-3,5-difluorophenol

Product 1

HCID 90843131Tert-butyl(4-tert-butyl-3,5-difluorophenoxy)acetateYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of sodium hydride (75 mg, 1.9 mmol) in THF (5 ml) was added 4-tert-butyl-3,5-difluorophenol (290 mg, 1.6 mmol) at 0° C., followed by stirring for 30 minutes. Then, tert-butyl bromoacetate (370 mg, 1.9 mmol) was added and the mixture was refluxed at 90° C. for 1 hour. The reaction was quenched with saturated ammonium chloride aqueous solution and the product was extracted with EtOAc, washed with brine, dried over magnesium sulfate. Then, filtration, evaporation, and purification through silica gel column chromatography eluting with hexane/EtOAc (20:1 to 4:1) gave the tert-butyl(4-tert-butyl-3,5-difluorophenoxy)acetate (403 mg, 86%). The DCM (2.0 ml) solution of tert-butyl(4-tert-butyl-3,5-difluorophenoxy)acetate (400 mg, 1.34 mmol) and TFA (2.0 ml), was stirred for 1 hour at room temperature. Evaporation gave the residue which was triturated with Hexane to furnish the title compound as a white solid (253 mg, 77%). 1H NMR (300 MHz, CDCl3): δ 1.42 (9H, t, J=2.2 Hz), 4.63 (2H, s), 6.39 (2H, d, J=12.1 Hz). MS (ESI) m/z 243 (M−H)−.

Workup

  1. customThe reaction was quenched with saturated ammonium chloride aqueous solution
  2. extractionthe product was extracted with EtOAc
  3. washwashed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationThen, filtration, evaporation, and purification through silica gel column chromatography
  6. washeluting with hexane/EtOAc (20:1 to 4:1)

Sources & evidence

ORD record
ord-7d54f6d518844c10aa281b59b1bc5c55
Source dataset
uspto-grants-2009_04
Patent number
US07514457B2

Reaction notes

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