Hydrochloric Acid → Ethyl 2,4,5-trifluorobenzoylacetate

HRID 1611445Notes

Reaction equation

HRID 1611445 reaction equation
CS(O)(=O)=[O:3].[F:6][C:7]1[CH:14]=[C:13]([F:15])[C:12]([F:16])=[CH:11][C:8]=1[C:9]#N.Br[CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20].Cl>[Zn].O1CCCC1>[F:6][C:7]1[CH:14]=[C:13]([F:15])[C:12]([F:16])=[CH:11][C:8]=1[C:9]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])=[O:3]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6395Methanesulfonic AcidHCID 7748Ethyl bromoacetateHCID 5938132,4,5-Trifluorobenzonitrile

Product 1

HCID 2758933Ethyl 2,4,5-trifluorobenzoylacetateYield 80%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

To a stirred suspension of 125 mg of zinc dust in 5.0. of tetrahydrofuran was added 11.0 mg of methanesulfonic acid and the mixture was heated at reflux. To the mixture was added 200 mg of 2,4,5-trifluorobenzonitrile, and subsequently 276 mg of ethyl bromoacetate was added dropwise over 1 hour. After the completion of the addition, the mixture was stirred at reflux for further 0.5 hour. The reaction mixture was cooled to 0 to 10° C., 1. of 3N aqueous hydrochloric acid solution was added, and the mixture was slowly warmed to room temperature. The reaction solution was stirred for 2 hours. Tetrahydrofuran was removed by distillation under reduced pressure. The residue was extracted with ethyl acetate and purified by silica gel column chromatography (eluent: ethylacetate/n-hexane= 1/10, v/v) to give the title compound in a yield of 80% (250 mg).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux
  3. additionwas added dropwise over 1 hour
  4. additionAfter the completion of the addition
  5. temperatureat reflux for further 0.5 hour
  6. temperaturethe mixture was slowly warmed to room temperature
  7. stirringThe reaction solution was stirred for 2 hours
  8. customTetrahydrofuran was removed by distillation under reduced pressure
  9. extractionThe residue was extracted with ethyl acetate
  10. custompurified by silica gel column chromatography (eluent

Sources & evidence

ORD record
ord-a955525ead5c496dbac3f2f18e1789f9
Source dataset
uspto-grants-2006_01
Patent number
US06987199B2

Reaction notes

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