Formic Acid → 2-[4-(tert-Butoxycarbonyl)benzyl]-4-[1-(2-ethoxy-2-oxoethyl)cyclopropyl]butanoic acid

HRID 1920590Notes

Reaction equation

HRID 1920590 reaction equation
C(N(CC)CC)C.C(O)=O.[C:11]([O:15][C:16]([C:18]1[CH:48]=[CH:47][C:21]([CH2:22][C:23]([CH2:36][CH2:37][C:38]2([CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH2:40][CH2:39]2)(C(OCC=C)=O)[C:24]([O:26]CC=C)=[O:25])=[CH:20][CH:19]=1)=[O:17])([CH3:14])([CH3:13])[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>[C:11]([O:15][C:16]([C:18]1[CH:48]=[CH:47][C:21]([CH2:22][CH:23]([CH2:36][CH2:37][C:38]2([CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH2:40][CH2:39]2)[C:24]([OH:26])=[O:25])=[CH:20][CH:19]=1)=[O:17])([CH3:13])([CH3:12])[CH3:14]

Participants

7

Reactant 4

HCID 284Formic AcidHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 57965749Diallyl [4-(tert-butoxycarbonyl)benzyl]{2-[1-(2-ethoxy-2-oxoethyl)cyclopropyl]ethyl}malonate

Product 1

HCID 579657452-[4-(tert-Butoxycarbonyl)benzyl]-4-[1-(2-ethoxy-2-oxoethyl)cyclopropyl]butanoic acid

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

At room temperature, a solution of 7.42 ml (53.56 mmol) of triethylamine and 1.53 ml (40 mmol) of formic acid in 25 ml of dioxane is added to a solution of 8.58 g (16.2 mmol) of diallyl [4-(tert-butoxycarbonyl)benzyl]{2-[1-(2-ethoxy-2-oxoethyl)cyclopropyl]ethyl}malonate, 298 mg (1.14 mmol) of triphenylphosphine and 73 mg (0.33 mmol) of palladium acetate in 75 ml of dioxane. The reaction mixture is then stirred at 100° C. for 2 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 (pH 4-5), and the organic phase is separated off. 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. The crude product obtained is purified by flash chromatography on silica gel (700 g; mobile phase: petroleum ether/ethyl acetate 1:1). This gives 4.9 g (74.6% of theory) of a colorless solid.

Workup

  1. temperatureAfter complete conversion, the reaction solution is cooled
  2. customthe solvent is removed under reduced pressure
  3. customthe organic phase is separated off
  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

Sources & evidence

ORD record
ord-d81ed0b128474404a0baf6cf7893e6c4
Source dataset
uspto-grants-2012_05
Patent number
US08168821B2

Reaction notes

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