Ethanol → Diethyl acetamide 2-(4-octanoyl phenyl)ethyl malonate

HRID 1595066Notes

Reaction equation

HRID 1595066 reaction equation
[C:1]([OH:7])(=[O:6])[CH2:2][C:3]([OH:5])=[O:4].[CH2:8]([CH:10]([CH2:14][CH3:15])[C:11]([NH2:13])=[O:12])[CH3:9].[H-].[Na+].[CH:18]([C:20]1[CH:25]=[CH:24][C:23]([C:26](=[O:34])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])=[CH:22][CH:21]=1)=[CH2:19].C(O)C>CN(C)C=O>[CH2:8]([CH:10]([CH2:14][CH3:15])[C:11]([NH2:13])=[O:12])[CH3:9].[C:1]([O:7][CH2:19][CH2:18][C:20]1[CH:25]=[CH:24][C:23]([C:26](=[O:34])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])=[CH:22][CH:21]=1)(=[O:6])[CH2:2][C:3]([O-:5])=[O:4]

Participants

6

Reactant 4

HCID 702EthanolHCID 24758Sodium hydrideHCID 125415361-(4-Ethenylphenyl)octan-1-oneHCID 22466969Diethyl acetamide malonate

Product 1

HCID 86757349Diethyl acetamide 2-(4-octanoyl phenyl)ethyl malonateYield 78.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4′-(2-Iodoethyl)octanophenone prepared (5 g) in the step D-3 was dissolved in anhydrous N,N-dimethylformamide (15 ml) to obtain 4′-(2-iodoethyl)octanophenone solution. Diethyl acetamide malonate (9.09 g) was dissolved in anhydrous N,N-dimethylformamide (30 ml) to obtain a solution to which 60% sodium hydride oil dispersion (1.23 g) was added with cooling. The solution was stirred under atmosphere of nitrogen for 1 hour. 4′-(2-Iodoethyl)octanophenone solution was added to the solution, and the solution was stirred under atmosphere of nitrogen at 60° C. for 2 hours. The reaction solution was poured into ice water, and extracted with ether, and washed with saturated saline solution. The extracted solution was dried over anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography using hexane-ethyl acetate (1:0→3:1) as an eluate to obtain diethyl acetamide-2-(4-octanoyl phenyl)ethyl malonate (3.2 g) and 4′-vinyl octanophenone (1.5 g) in the form of colorless crystal, respectively. The diethyl acetamide malonate (4.25 g) was dissolved in anhydrous N,N-dimethylformamide (30 ml) to obtain a solution, to which 60% sodium hydride oil dispersion (574 mg) was added. The solution was stirred under atmosphere of nitrogen at room temperature for 30 minutes. 4′-Vinyl octanophenone (1.5 g) and anhydrous ethanol (7.5 ml) were added to the solution, and the solution was stirred under atmosphere of nitrogen at 60° C. for 6 hours, and the solution was stirred at room temperature for 2 days. The reaction solution was poured into ice water, extracted with ether, and washed with saturated saline solution. The extracted solution was dried over anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography using hexane-ethyl acetate (1:0→4:1) as an eluate to obtain diethyl acetamide-2-(4-octanoyl phenyl)ethyl malonate (2.29 g) in the form of colorless crystal.

Workup

  1. customto obtain a solution
  2. stirringthe solution was stirred under atmosphere of nitrogen at 60° C. for 6 hours
  3. stirringthe solution was stirred at room temperature for 2 days
  4. extractionextracted with ether
  5. washwashed with saturated saline solution
  6. dry with materialThe extracted solution was dried over anhydrous magnesium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-c8678d29c1e14583b08a9eb4bf583347
Source dataset
uspto-grants-2001_09
Patent number
US06284915B1

Reaction notes

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