Hydrochloric Acid → Ethyl (2-chloro-6-fluorophenyl)acetoacetate

HRID 1348548Notes

Reaction equation

HRID 1348548 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:5]=1[CH2:11][C:12]([O:14]CC)=O.[C:17]([O:20][C:21](=O)[CH3:22])(=[O:19])[CH3:18].Cl>O1CCCC1>[Cl:3][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:5]=1[CH2:11][C:12](=[O:14])[CH2:18][C:17]([O:20][CH2:21][CH3:22])=[O:19]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7918Acetic AnhydrideHCID 24758Sodium hydrideHCID 2733231Ethyl 2-chloro-6-fluorophenylacetate

Product 1

HCID 63022492Ethyl (2-chloro-6-fluorophenyl)acetoacetateYield 35.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Into a mixture of 9.6 g of sodium hydride (60% in oil) and 200 ml of tetrahydrofuran, 21.7 g of ethyl 2-chloro-6-fluorophenylacetate were added dropwise under reflux. Then, a solution of 12.3 g of acetic anhydride in 40 ml tetrahydrofuran was added thereto and refluxed under heating for 10 hours. The reaction mixture was cooled, poured into iced dil. hydrochloric acid and extracted with t-butyl methyl ether. The organic layer was washed with dil. hydrochloric acid, aqueous saturated sodium bicarbonate solution, dil. hydrochloric acid and water, subsequently, dried over sodium sulfate and concentrated. The residue was subjected to silica gel column chromatography to give 9.27 g of ethyl (2-chloro-6-fluorophenyl)acetoacetate.

Workup

  1. additionwere added dropwise
  2. temperatureunder reflux
  3. temperaturerefluxed
  4. temperatureunder heating for 10 hours
  5. temperatureThe reaction mixture was cooled
  6. extractionextracted with t-butyl methyl ether
  7. washThe organic layer was washed with dil. hydrochloric acid, aqueous saturated sodium bicarbonate solution, dil. hydrochloric acid and water
  8. dry with materialsubsequently, dried over sodium sulfate
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-422d960a922041c29902827a1bcca0d3
Source dataset
uspto-grants-2007_05
Patent number
US07211545B2

Reaction notes

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