Formic Acid → Methyl 4-(3-carboxy-7-cyanoheptyl)benzoate

HRID 1927424Notes

Reaction equation

HRID 1927424 reaction equation
C(N(CC)CC)C.C(O)=O.[C:11]([CH2:13][CH2:14][CH2:15][CH2:16][C:17]([CH2:30][CH2:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]([O:40][CH3:41])=[O:39])=[CH:34][CH:33]=1)(C(OCC=C)=O)[C:18]([O:20]CC=C)=[O:19])#[N: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:18]([CH:17]([CH2:16][CH2:15][CH2:14][CH2:13][C:11]#[N:12])[CH2:30][CH2:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]([O:40][CH3:41])=[O:39])=[CH:34][CH:33]=1)([OH:20])=[O:19]

Participants

7

Reactant 4

HCID 284Formic AcidHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 57831337Diallyl 2-(4-cyanobutyl)-2-[2-(4-methoxycarbonylphenyl)ethyl]malonate

Product 1

HCID 57831399Methyl 4-(3-carboxy-7-cyanoheptyl)benzoate

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A solution of 7.45 ml (53.42 mmol) of triethylamine and 1.53 ml (40.47 mmol) of formic acid in 67 ml of dioxane is added to a solution of 6.92 g (16.19 mmol) of diallyl 2-(4-cyanobutyl)-2-[2-(4-methoxycarbonylphenyl)ethyl]malonate, 594 mg (2.26 mmol) of triphenylphosphine and 145 mg (0.64 mmol) of palladium acetate in 67 ml of dioxane at room temperature. The reaction mixture is then stirred at 100° C. for 12 hours. After conversion is complete, the reaction solution is cooled and the solvent is removed in vacuo. The residue is taken up in ethyl acetate and water and acidified with 1 N hydrochloric acid, 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 in vacuo. The resulting crude product is purified by flash chromatography on silica gel [mobile phase: cyclohexane/ethyl acetate (with 1% formic acid) 2:1→1:3]. 2.1 g (43% of theory) of a colorless solid are obtained.

Workup

  1. temperaturethe reaction solution is cooled
  2. customthe solvent is removed in vacuo
  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 in vacuo
  9. customThe resulting crude product is purified by flash chromatography on silica gel [mobile phase: cyclohexane/ethyl acetate (with 1% formic acid) 2:1→1:3]
  10. custom2.1 g (43% of theory) of a colorless solid are obtained

Sources & evidence

ORD record
ord-acac0867888243c592df126af4e6d3c9
Source dataset
uspto-grants-2012_05
Patent number
US08183271B2

Reaction notes

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