Trifluoroacetic acid → (4-tert-Butyl-3,5-difluorophenoxy)acetic acid

HRID 2108830

Reaction equation

HRID 2108830 reaction equation
C([O:5][C:6](=[O:21])[CH2:7][O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([C:16]([CH3:19])([CH3:18])[CH3:17])=[C:11]([F:20])[CH:10]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:16]([C:12]1[C:11]([F:20])=[CH:10][C:9]([O:8][CH2:7][C:6]([OH:21])=[O:5])=[CH:14][C:13]=1[F:15])([CH3:19])([CH3:17])[CH3:18]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90843131Tert-butyl(4-tert-butyl-3,5-difluorophenoxy)acetate

Product 1

HCID 68804332(4-tert-Butyl-3,5-difluorophenoxy)acetic acidYield 77.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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. customEvaporation
  2. customgave the residue which
  3. customwas triturated with Hexane

Sources & evidence

ORD record
ord-4904f02467ca4b218176eaef9d593c9f
Source dataset
uspto-grants-2009_04
Patent number
US07514457B2

Linked notes

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