Benzene → Ethyl alpha-(2,5-dimethoxybenzyl)acetoacetate

HRID 620024Notes

Reaction equation

HRID 620024 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:4]=1[CH:5]=O.[C:13]([O:19][CH2:20][CH3:21])(=[O:18])[CH2:14][C:15]([CH3:17])=[O:16].C1C=CC=CC=1.N1CCCCC1>C(O)(=O)C>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:4]=1[CH2:5][CH:14]([C:15]([CH3:17])=[O:16])[C:13]([O:19][CH2:20][CH3:21])=[O:18]

Participants

6

Reactant 4

HCID 241BenzeneHCID 8082PiperidineHCID 8868Ethyl AcetoacetateHCID 667262,5-Dimethoxybenzaldehyde

Product 1

HCID 12597482Ethyl alpha-(2,5-dimethoxybenzyl)acetoacetate

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 2,5-dimethoxybenzaldehyde (100 g), ethyl acetoacetate (84.5 g), anhydrous benzene (200 ml), piperidine (6 ml) and acetic acid (12 ml) was heated at reflux for 3 hours in an apparatus fitted with a Dean-Stark trap to collect the azeotropically distilled water. The reaction mixture was cooled, benzene (300 ml) added, and the solution was washed successively with water (100 ml), cooled 0.1N hydrochloric acid (200 ml), 5% aqueous sodium bicarbonate (200 ml) and dilute acetic acid (100 ml) and dried over anhydrous magnesium sulfate. The solvent was then removed under reduced pressure and the residual oil distilled, b.p. 169°-170° C./0.3 mm Hg. The product, ethyl α-(2,5-dimethoxybenzylidene)acetoacetate, solidified on standing (104 g, m.p. 68°-69° C.) and was recrystallised from ethanol-pentane (m.p. 72°-73° C.). A portion (38 g) of the product was reduced catalytically in the presence of palladium on charcoal catalyst (Pd/C) in ethyl acetate (150 ml). The product, after removal of solvent, was purified by distillation under reduced pressure to give ethyl α-(2,5-dimethoxybenzyl)acetoacetate, b.p. 146°-148° C./0.3 mm Hg.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3 hours in an apparatus
  3. customfitted with a Dean-Stark trap
  4. distillationto collect the azeotropically distilled water
  5. temperatureThe reaction mixture was cooled
  6. additionbenzene (300 ml) added
  7. washthe solution was washed successively with water (100 ml)
  8. temperaturecooled 0.1N hydrochloric acid (200 ml), 5% aqueous sodium bicarbonate (200 ml) and dilute acetic acid (100 ml)
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customThe solvent was then removed under reduced pressure
  11. distillationthe residual oil distilled
  12. customwas recrystallised from ethanol-pentane (m.p. 72°-73° C.)
  13. customThe product, after removal of solvent
  14. distillationwas purified by distillation under reduced pressure

Sources & evidence

ORD record
ord-d6354d9973134daf918f1a081a759de5
Source dataset
uspto-grants-1989_04
Patent number
US04818759

Reaction notes

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