Triethylamine → Ethyl 2,4,5-trifluorobenzoylacetate

HRID 1601885Notes

Reaction equation

HRID 1601885 reaction equation
[C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([O-:5])=O.[K+].[Cl-].[Mg+2].[Cl-].C(N(CC)CC)C.[F:21][C:22]1[CH:30]=[C:29]([F:31])[C:28]([F:32])=[CH:27][C:23]=1C(Cl)=O>C(#N)C>[CH2:8]([O:7][C:1](=[O:6])[CH2:2][C:3](=[O:5])[C:23]1[CH:27]=[C:28]([F:32])[C:29]([F:31])=[CH:30][C:22]=1[F:21])[CH3:9]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 1451642,4,5-Trifluorobenzoyl chlorideHCID 3446434Potassium ethyl malonateHCID 5360315Magnesium Chloride

Product 1

HCID 2758933Ethyl 2,4,5-trifluorobenzoylacetateYield 94%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To an oven-dried flask was added potassium ethyl malonate (3.66 g, 21.5 mmol) and freshly distilled acetonitrile (70 mL). The mixture was cooled to 10° C. to 15° C. and stirred under an atmosphere of nitrogen and to it added anhydrous magnesium chloride (2.44 g, 25.7 mmol) and triethylamine (2.05 g, 20.3 mmol). The mixture was then stirred at room temperature under nitrogen for 2.5 hours. The resultant white slurry was recooled to 0° C. and 2,4,5-trifluorobenzoyl chloride was added over a period of 15 minutes, followed by more triethylamine (0.23 g, 2.3 mmol). The mixture was then stirred at room temperature overnight under nitrogen. Acetonitrile was then removed in vacuo and toluene (30 mL) was added. The mixture was reconcentrated and more toluene (60 mL) then added. Hydrochloric acid (1.5 M, 40 mL) was cautiously added, ensuring that the temperature did not exceed 25° C., and the aqueous layer separated. The organic fraction was washed with 1.5 M HCl (2×25 mL) and water (2×25 mL), dried over MgSO4, and solvent removed in vacuo to afford 3-oxo-3-(2,4,5-trifluoro-phenyl)-propionic acid ethyl ester as a pale orange solid (2.35 g, 9.55 mmol, 94%).

Workup

  1. temperatureThe mixture was cooled to 10° C. to 15° C.
  2. stirringThe mixture was then stirred at room temperature under nitrogen for 2.5 hours
  3. customwas recooled to 0° C.
  4. stirringThe mixture was then stirred at room temperature overnight under nitrogen
  5. customAcetonitrile was then removed in vacuo and toluene (30 mL)
  6. additionwas added
  7. additionmore toluene (60 mL) then added
  8. additionHydrochloric acid (1.5 M, 40 mL) was cautiously added
  9. customdid not exceed 25° C.
  10. customthe aqueous layer separated
  11. washThe organic fraction was washed with 1.5 M HCl (2×25 mL) and water (2×25 mL)
  12. dry with materialdried over MgSO4, and solvent
  13. customremoved in vacuo

Sources & evidence

ORD record
ord-541383899ede466ab89e7e07508e561b
Source dataset
uspto-grants-1999_11
Patent number
US05977400

Reaction notes

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