Diethyl Ether → 2-[2-Fluoro-4-(furan-2-ylmethyl)-phenyl]propionic acid

HRID 1506870Notes

Reaction equation

HRID 1506870 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([CH3:14])[C:10]([O:12]C)=[O:11])=[C:5]([F:15])[CH:4]=1.[O:16]1[CH:20]=[CH:19][CH:18]=[C:17]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].CCOCC>O1CCCC1.C1C(=O)[N-]C(=O)C1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Br[Pd+]>[F:15][C:5]1[CH:4]=[C:3]([CH2:2][C:17]2[O:16][CH:20]=[CH:19][CH:18]=2)[CH:8]=[CH:7][C:6]=1[CH:9]([CH3:14])[C:10]([OH:12])=[O:11]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 10340Sodium CarbonateHCID 2734357Furan-2-boronic acidHCID 49837497Methyl 2-[4-(bromomethyl)-2-fluorophenyl]-propionate

Product 1

HCID 601555312-[2-Fluoro-4-(furan-2-ylmethyl)-phenyl]propionic acidYield 45.3%

Reagents, catalysts & solvents 2

HCID 11434313trans-Bromo(N-succinimidyl)bis(triphenylphosphine)palladium(II)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

Compound 20 (0.88 g, 3.2 mmol) and 2-furan boronic acid (0.54 g, 4.8 mmol) were dissolved in tetrahydrofuran (12 mL) and a 2 M-aqueous solution (4.0 mL) of sodium carbonate. To this solution, trans-bromo(N-succinimidyl)bis(triphenylphosphine)palladium(II) [trans-PdBr(N-Succ)(PPh3)2] (25.9 mg, 1.0 mol %) was added and heated to reflux for 3 hours. After cooling to room temperature and adding ether (50 mL) to the solution, the organic layer was washed with water (30 mL) and dried (over magnesium sulfate), and the solvent was distilled off. The obtained residue was subjected to silica gel column chromatography and elution with an n-hexane/ethyl acetate (20:1) solution followed by conventional hydrolysis with potassium hydroxide to give 0.36 g (43%) of compound (21a) of interest as white solid.

Workup

  1. temperatureheated
  2. temperatureto reflux for 3 hours
  3. washthe organic layer was washed with water (30 mL)
  4. dry with materialdried (over magnesium sulfate)
  5. distillationthe solvent was distilled off
  6. washThe obtained residue was subjected to silica gel column chromatography and elution with an n-hexane/ethyl acetate (20:1) solution
  7. customfollowed by conventional hydrolysis with potassium hydroxide

Sources & evidence

ORD record
ord-7b87ed0f4bce44fe83e2308b9d64daad
Source dataset
uspto-grants-2015_12
Patent number
US09221786B2

Reaction notes

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