1-(Phenylmethyl) butanedioate → N-{2-t-Butyl-5-[3-(benzyloxycarbonyl)propionylaminocarbonyl]phenyl}-3-(2,4-dimethoxyphenyl)octanamide

HRID 1637456Notes

Reaction equation

HRID 1637456 reaction equation
[C:1]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)(=[O:7])[CH2:2][CH2:3][C:4]([OH:6])=O.[C:16]([C:20]1[CH:25]=[CH:24][C:23]([C:26](=[O:28])[NH2:27])=[CH:22][C:21]=1[NH:29][C:30](=[O:48])[CH2:31][CH:32]([C:38]1[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[CH:40][C:39]=1[O:46][CH3:47])[CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])([CH3:19])([CH3:18])[CH3:17]>C(#N)C.C(OCC)(=O)C>[C:16]([C:20]1[CH:25]=[CH:24][C:23]([C:26]([NH:27][C:4](=[O:6])[CH2:3][CH2:2][C:1]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])=[O:28])=[CH:22][C:21]=1[NH:29][C:30](=[O:48])[CH2:31][CH:32]([C:38]1[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[CH:40][C:39]=1[O:46][CH3:47])[CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])([CH3:17])([CH3:18])[CH3:19]

Participants

5

Reactant 2

HCID 87881-(Phenylmethyl) butanedioateHCID 19348437N-(2-t-Butyl-5-carbamoylphenyl)-3-(2,4-dimethoxyphenyl)octanamide

Product 1

HCID 19348743N-{2-t-Butyl-5-[3-(benzyloxycarbonyl)propionylaminocarbonyl]phenyl}-3-(2,4-dimethoxyphenyl)octanamideYield 15%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

810 mg (5.0 mmol) of N,N'-carbonyldiimidazole were added to a solution of 1.04 g (5.0 mmol) of benzyl hydrogen succinate in 10 ml of acetonitrile, and the resulting mixture was stirred for 15 minutes, after which 565 mg (1.22 mmol) of N-(2-t-butyl-5-carbamoylphenyl)-3-(2,4-dimethoxyphenyl)octanamide (prepared as described in Example 2) and 610 mg (5.0 mmol) of 4-N,N-dimethylaminopyridine were added. The mixture was then heated under reflux for 4 days, after which the reaction mixture was allowed to cool to room temperature. The reaction mixture was then diluted with ethyl acetate, and the diluted solution was washed with 2 N aqueous hydrochloric acid and with 2 a saturated aqueous solution of sodium chloride, in that order, after which it was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by column chromatography through 15 g of silica gel using a gradient elution method, with mixtures of hexane and ethyl acetate ranging from 3:1 to 1:1 by volume as the eluent, to give a crude product containing the title compound. The product was further purified by column chromatography through silica gel under the same conditions as above, to give the title compound as a viscous substance in a 15% yield.

Workup

  1. temperatureThe mixture was then heated
  2. temperatureunder reflux for 4 days
  3. washthe diluted solution was washed with 2 N aqueous hydrochloric acid and with 2 a saturated aqueous solution of sodium chloride
  4. dry with materialin that order, after which it was dried over anhydrous sodium sulfate
  5. customThe solvent was removed by distillation under reduced pressure
  6. customthe resulting residue was purified by column chromatography through 15 g of silica gel using
  7. washa gradient elution method
  8. customwith mixtures of hexane and ethyl acetate ranging from 3:1 to 1:1 by volume as the eluent, to give a crude product

Sources & evidence

ORD record
ord-b20e508b2c044559a435c608b73a44e6
Source dataset
uspto-grants-2000_03
Patent number
US06040339

Reaction notes

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