Potassium Carbonate → 2-[4-(Ethyl-3-oxobutyl)-2-fluoro-phenyl]propionic acid

HRID 1506874Notes

Reaction equation

HRID 1506874 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH2:7]([CH:9]([C:15]([CH3:17])=[O:16])C(OCC)=O)[CH3:8].Br[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]([CH3:31])[C:27]([O:29]C)=[O:28])=[C:22]([F:32])[CH:21]=1>CC(C)=O>[CH2:7]([CH2:9][C:15](=[O:16])[CH2:17][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]([CH3:31])[C:27]([OH:29])=[O:28])=[C:22]([F:32])[CH:21]=1)[CH3:8]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 79065Butanoic acid, 2-ethyl-3-oxo-, ethyl esterHCID 49837497Methyl 2-[4-(bromomethyl)-2-fluorophenyl]-propionate

Product 1

HCID 1176761982-[4-(Ethyl-3-oxobutyl)-2-fluoro-phenyl]propionic acidYield 59.9%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a suspension of anhydrous potassium carbonate (0.86 g, 6.2 mmol) in acetone (40 mL), ethyl 2-ethylacetoacetate (0.56 mL, 3.45 mmol) was added under stirring. After stirring for 15 minutes at room temperature, compound (20) (0.95 g, 3.45 mmol) was added, and the reaction mixture was refluxed for 12 hours. After cooling, the reaction mixture was concentrated under reduced pressure, and the residue was treated with dichloromethane (50 mL). The organic layer was washed with a sodium bicarbonate solution and saline, and the solvent was distilled off. The obtained residue was subjected to silica gel column chromatography and elution with an n-hexane/ethyl acetate (7:2) solution followed by conventional decarboxylation and hydrolysis to give 0.55 g (45%) of compound (23) of interest as clear colorless oil.

Workup

  1. additionwas added
  2. stirringAfter stirring for 15 minutes at room temperature
  3. temperaturethe reaction mixture was refluxed for 12 hours
  4. temperatureAfter cooling
  5. concentrationthe reaction mixture was concentrated under reduced pressure
  6. additionthe residue was treated with dichloromethane (50 mL)
  7. washThe organic layer was washed with a sodium bicarbonate solution and saline
  8. distillationthe solvent was distilled off
  9. washThe obtained residue was subjected to silica gel column chromatography and elution with an n-hexane/ethyl acetate (7:2) solution
  10. customfollowed by conventional decarboxylation and hydrolysis

Sources & evidence

ORD record
ord-5de0fbda7c14446fb8e0ba1e2f8f837b
Source dataset
uspto-grants-2015_12
Patent number
US09221786B2

Reaction notes

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