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

HRID 2300835Notes

Reaction equation

HRID 2300835 reaction equation
[C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([O-:5])=O.[K+].C(N(CC)CC)C.[Mg+2].[Cl-].[Cl-].[CH3:21][C:22]1[CH:30]=[CH:29][C:25](C(Cl)=O)=[CH:24][CH:23]=1>C(#N)C>[CH3:21][C:22]1[CH:30]=[CH:29][C:25]([C:3]([CH2:2][C:1]([O:7][CH2:8][CH3:9])=[O:6])=[O:5])=[CH:24][CH:23]=1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 134054-Methylbenzoyl ChlorideHCID 3446434Potassium ethyl malonateHCID 5360315Magnesium Chloride

Product 1

HCID 292637Ethyl 3-(4-methylphenyl)-3-oxopropanoate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred suspension of potassium ethyl malonate (1.62 g, 9.51 mmol, 2.1 eq) in acetonitrile (14 mL) at 10° C. under nitrogen was added triethylamine (1.8 mL) followed by MgCl2 (1.1 g, 11.3 mmol, 2.5 eq). The mixture was allowed to stir at room temperature for 2.5 hours. The mixture was cooled to 0° C. and 4-methylbenzoyl chloride (700 mg, 4.53 mmol, 1 eq) was added dropwise over 15 minutes followed by addition of triethylamine (0.3 mL). The mixture was allowed to warm to room temperature and was stirred overnight. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate and cooled to 10° C. The solution was washed (cautiously) with 4N aqueous HCl. The aqueous layer was back extracted with ethyl acetate. The organic extracts were combined, washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was dissolved in aqueous 2N NaOH and extracted 3× with diethyl ether. The ether extracts were combined, washed with water, then brine, dried over anhydrous Na2SO4, filtered and concentrated. The title compound was used in the next step without further purification.

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. temperatureto warm to room temperature
  3. stirringwas stirred overnight
  4. customThe solvent was removed under reduced pressure
  5. dissolutionThe residue was dissolved in ethyl acetate
  6. temperaturecooled to 10° C
  7. washThe solution was washed (cautiously) with 4N aqueous HCl
  8. extractionThe aqueous layer was back extracted with ethyl acetate
  9. washwashed with water and brine
  10. dry with materialdried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. dissolutionThe residue was dissolved in aqueous 2N NaOH
  14. extractionextracted 3× with diethyl ether
  15. washwashed with water
  16. dry with materialbrine, dried over anhydrous Na2SO4
  17. filtrationfiltered
  18. concentrationconcentrated
  19. customThe title compound was used in the next step without further purification

Sources & evidence

ORD record
ord-8a9595f605ae43a5aea30f9a3a12f515
Source dataset
uspto-grants-2002_12
Patent number
US06498165B1

Reaction notes

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