Acetamidomalonic acid diethyl ester → Diethyl acetamido[2-(2-nitrophenyl)ethyl]propanedioate

HRID 482727Notes

Reaction equation

HRID 482727 reaction equation
[C:1]([NH:4][CH:5]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:3])[CH3:2].[O-]CC.[Na+].[N+:20]([C:23]1[CH:31]=[CH:30][CH:29]=[CH:28][C:24]=1[CH2:25][CH2:26]Br)([O-:22])=[O:21]>C(O)C>[C:1]([NH:4][C:5]([CH2:26][CH2:25][C:24]1[CH:28]=[CH:29][CH:30]=[CH:31][C:23]=1[N+:20]([O-:22])=[O:21])([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 14041Acetamidomalonic acid diethyl esterHCID 2723922Sodium ethoxideHCID 123638782-Nitrophenethyl bromide

Product 1

HCID 20244794Diethyl acetamido[2-(2-nitrophenyl)ethyl]propanedioate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Procedure

A solution of diethyl acetamidomalonate (33.2 g) in ethanol (150 ml) was added to a solution of sodium ethoxide in ethanol [prepared from sodium (3.8 g) and ethanol (200 ml)]. The reaction mixture was stirred at room temperature for 30 minutes and a solution of 2-nitrophenethyl bromide (J. Med. Chem. 20, 1020 (1977), 40.0 g) in ethanol (100 ml) was added dropwise during 20 minutes. After addition was complete, the reaction mixture was refluxed for 18 hours, then cooled to room temperature and evaporated under reduced pressure. The residue was dissolved in water (350 ml) and the solution extracted with ethyl acetate (2×350 ml). The combined ethyl acetate extracts were washed with water (200 ml) and dried over magnesium sulfate. Removal of the solvent under reduced pressure gave diethyl 2-acetamido-2-(o-nitrophenethyl)malonate as a low melting solid, used without further purification for the next synthetic step.

Workup

  1. additionAfter addition
  2. temperaturethe reaction mixture was refluxed for 18 hours
  3. temperaturecooled to room temperature
  4. customevaporated under reduced pressure
  5. dissolutionThe residue was dissolved in water (350 ml)
  6. extractionthe solution extracted with ethyl acetate (2×350 ml)
  7. washThe combined ethyl acetate extracts were washed with water (200 ml)
  8. dry with materialdried over magnesium sulfate
  9. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-34e0cfdd8f8641408381c35d4a444ab2
Source dataset
uspto-grants-1986_03
Patent number
US04575503

Reaction notes

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