Water → 1,3-Bis(phenylmethyl) 2-(2-methoxyethyl)propanedioate

HRID 1613479Notes

Reaction equation

HRID 1613479 reaction equation
[C:1]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)(=[O:13])[CH2:2][C:3]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].[H-].[Na+].[CH3:24][O:25][CH2:26][CH2:27]Br.O>O1CCCC1>[CH2:6]([O:5][C:3](=[O:4])[CH:2]([CH2:27][CH2:26][O:25][CH3:24])[C:1]([O:14][CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[O:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 809722-Bromoethyl methyl etherHCID 84754Dibenzyl malonate

Product 1

HCID 541445511,3-Bis(phenylmethyl) 2-(2-methoxyethyl)propanedioateYield 45.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Dibenzyl malonate (28.43 g, 0.1 mole) was added dropwise over 1 hour to a stirred suspension of sodium hydride (3.15 g, 80% dispersion in oil; 0.105 mole) in dry tetrahydrofuran (100 ml) under nitrogen, the temperature being allowed to rise to 40° C. 2-Methoxyethyl bromide (13.9 g, 0.1 mole) was added to the resulting clear solution, which was stirred at room temperature for two hours, and then refluxed overnight. Water was added, and the mixture extracted with methylene chloride. The organic extract on washing with water, drying (MgSO4) and evaporation under vacuum gave a crude liquid (30.94 g). Chromatography on silica gel (700 g) eluting with a mixture of ether and hexane (2:8 by volume) gave 2-methoxyethyl-malonic acid dibenzyl ester as a colourless liquid (15.6 g). This was dissolved in dioxan (150 ml) and a solution of potassium hydroxide (2.55 g, 45.44 mmole) in water (40 ml) added at 0° C. with stirring. The mixture was stirred overnight at room temperature and the solvent was evaporated under vacuum. Water was added and the mixture was extracted with ether to remove unreacted diester. The aqueous phase was then acidified with 2N hydrochloric acid (50 ml) and extracted with ether. The organic extract on washing with water, drying (MgSO4) and evaporation under vacuum gave the mono-ester as a colourless oil (8.95 g, 78%).

Workup

  1. customto rise to 40° C
  2. temperaturerefluxed overnight
  3. extractionthe mixture extracted with methylene chloride
  4. extractionThe organic extract
  5. washon washing with water
  6. customdrying
  7. custom(MgSO4) and evaporation under vacuum
  8. customgave a crude liquid (30.94 g)
  9. washChromatography on silica gel (700 g) eluting with a mixture of ether and hexane (2:8 by volume)

Sources & evidence

ORD record
ord-e72b6ef2420f4493b926d5936e9659ff
Source dataset
uspto-grants-1993_03
Patent number
US05192800

Reaction notes

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