Formic Acid → 4-[1-(2-Ethoxy-2-oxoethyl)cyclopropyl]-2-{2-[4-(methoxycarbonyl)phenyl]ethyl}butanoic acid

HRID 1920576Notes

Reaction equation

HRID 1920576 reaction equation
C(N(CC)CC)C.C(O)=O.[CH2:11]([O:13][C:14](=[O:46])[CH2:15][C:16]1([CH2:19][CH2:20][C:21]([CH2:34][CH2:35][C:36]2[CH:41]=[CH:40][C:39]([C:42]([O:44][CH3:45])=[O:43])=[CH:38][CH:37]=2)(C(OCC=C)=O)[C:22]([O:24]CC=C)=[O:23])[CH2:18][CH2:17]1)[CH3:12].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:11]([O:13][C:14](=[O:46])[CH2:15][C:16]1([CH2:19][CH2:20][CH:21]([CH2:34][CH2:35][C:36]2[CH:37]=[CH:38][C:39]([C:42]([O:44][CH3:45])=[O:43])=[CH:40][CH:41]=2)[C:22]([OH:24])=[O:23])[CH2:18][CH2:17]1)[CH3:12]

Participants

7

Reactant 4

HCID 284Formic AcidHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 57965761Diallyl {2-[1-(2-ethoxy-2-oxoethyl)cyclopropyl]ethyl}{2-[4-(methoxycarbonyl)phenyl]ethyl}-malonate

Product 1

HCID 579657474-[1-(2-Ethoxy-2-oxoethyl)cyclopropyl]-2-{2-[4-(methoxycarbonyl)phenyl]ethyl}butanoic acid

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

At room temperature a solution of 0.6 ml (4.3 mmol) of triethylamine and 0.12 ml (3.25 mmol) of formic acid in 15 ml of dioxane is added to a solution of 650 mg (1.3 mmol) of diallyl {2-[1-(2-ethoxy-2-oxoethyl)cyclopropyl]ethyl}{2-[4-(methoxycarbonyl)phenyl]ethyl}malonate, 24 mg (0.09 mmol) of triphenylphosphine and 6 mg (0.026 mmol) of palladium acetate in 15 ml of dioxane. The reaction mixture is then stirred at 100° C. for 12 hours. After complete conversion, the reaction solution is cooled and the solvent is removed under reduced pressure. The residue is then taken up in ethyl acetate and water and acidified with 1 N hydrochloric acid, and the organic phase is removed. The aqueous phase is extracted three more times with ethyl acetate, and the organic phases are then combined, washed with saturated sodium chloride solution and dried over sodium sulfate. After filtration, the solution is concentrated under reduced pressure and the residue is purified by flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 4:1). This gives 406 mg (83% of theory) of a yellow oil.

Workup

  1. temperatureAfter complete conversion, the reaction solution is cooled
  2. customthe solvent is removed under reduced pressure
  3. customthe organic phase is removed
  4. extractionThe aqueous phase is extracted three more times with ethyl acetate
  5. washwashed with saturated sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. filtrationAfter filtration
  8. concentrationthe solution is concentrated under reduced pressure
  9. customthe residue is purified by flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 4:1)

Sources & evidence

ORD record
ord-2d4ae3fc8d8d4aa1bd3fdc80e110c925
Source dataset
uspto-grants-2012_05
Patent number
US08168821B2

Reaction notes

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