Ethyl Acetoacetate → Ethyl 3-(4-methylphenyl)-3-oxopropanoate

HRID 747830Notes

Reaction equation

HRID 747830 reaction equation
[OH-].[Na+].[C:3]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:4][C:5]([CH3:7])=[O:6].[CH3:12][C:13]1[CH:21]=[CH:20]C(C(Cl)=O)=[CH:15][CH:14]=1>O.C1(C)C=CC=CC=1>[CH3:12][C:13]1[CH:21]=[CH:20][C:7]([C:5]([CH2:4][C:3]([O:9][CH2:10][CH3:11])=[O:8])=[O:6])=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 8868Ethyl AcetoacetateHCID 134054-Methylbenzoyl ChlorideHCID 14798Sodium Hydroxide2×

Product 1

HCID 292637Ethyl 3-(4-methylphenyl)-3-oxopropanoateYield 35%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

Sodium hydroxide solution (33%, 32.5 ml) was added to ethyl acetoacetate (97.5 g, 750 mmol) in a mixture of water (250 ml) and toluene (12 ml) at 0-5° C. under stirring (pH 11). After 30 minutes 4-methylbenzoylchloride (127.46 g, 825 mmol) and sodium hydroxide solution (33%, 135 ml) was added simultaneously over a period two hours. The reaction mixture was stirred for 15 minutes at 0° C. and for 1 hour at 35° C. Aqueous layer was separated, ammonium chloride (40 g) was added and stirred slowly over night. The reaction mixture was saturated with sodium chloride and extracted with ethyl acetate. The ethyl acetate extract was washed with water, dried over anhydrous sodium sulphate and concentrated to dryness in vacuum. The crude product thus obtained was purified by column chromatography to yield the title compound as viscous oil (54 g, 35%). MS m/z: 207.1 (M+).

Workup

  1. stirringThe reaction mixture was stirred for 15 minutes at 0° C. and for 1 hour at 35° C
  2. customAqueous layer was separated
  3. additionammonium chloride (40 g) was added
  4. stirringstirred slowly over night
  5. extractionextracted with ethyl acetate
  6. extractionThe ethyl acetate extract
  7. washwas washed with water
  8. dry with materialdried over anhydrous sodium sulphate
  9. concentrationconcentrated to dryness in vacuum
  10. customThe crude product thus obtained
  11. customwas purified by column chromatography

Sources & evidence

ORD record
ord-9238b81ba58e40f3b8b8375e863fbc11
Source dataset
uspto-grants-2008_07
Patent number
US07399760B2

Reaction notes

Loading…