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

HRID 1672679Notes

Reaction equation

HRID 1672679 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)benzoateYield 43%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
10 °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 from Example 91A, 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 10° 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 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 organic phase is concentrated in vacuo. The resulting crude product is purified by flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 2:1→1:3, with 1% formic acid). 2.1 g (43% yield, 100% purity) 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 times with ethyl acetate
  5. washwashed with saturated sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. filtrationAfter filtration
  8. concentrationthe organic phase is concentrated in vacuo
  9. customThe resulting crude product is purified by flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 2:1→1:3, with 1% formic acid)
  10. custom2.1 g (43% yield, 100% purity) of a colorless solid are obtained

Sources & evidence

ORD record
ord-afe4d893a0dc4962add6a544bf223666
Source dataset
uspto-grants-2011_08
Patent number
US07998988B2

Reaction notes

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