Sulfuric Acid → Ethyl 4,4-difluoroacetoacetate

HRID 2283188Notes

Reaction equation

HRID 2283188 reaction equation
[H-].[Na+].C([O:6][CH2:7][CH:8]([F:10])[F:9])(=O)C.[C:11]([O:14][CH2:15][CH3:16])(=[O:13])[CH3:12].S(=O)(=O)(O)O>O1CCCC1>[F:9][CH:8]([F:10])[C:7](=[O:6])[CH2:12][C:11]([O:14][CH2:15][CH3:16])=[O:13]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 1370742,2-Difluoroethylacetate

Product 1

HCID 67697Ethyl 4,4-difluoroacetoacetate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Under a nitrogen atmosphere, 46.7 g (1.168 mol) of sodium hydride (60% dispersion in paraffin) were added to 600 ml of tetrahydrofuran. A mixture of 125 g (1.008 mol) of difluoroethyl acetate and 88.7 g (1.010 mol) of ethyl acetate was added dropwise at 35° C., while the temperature was kept below 40° C. The mixture was then further stirred at room temperature overnight. The reaction mixture was carefully poured into 1.7 l of ice water and the pH adjusted to pH 3 by addition of sulphuric acid. The mixture was extracted twice, each time with 500 ml of methyl tert-butyl ether, and the combined organic phases were washed twice with saturated sodium chloride solution, dried over sodium sulphate, concentrated at 40° C. and 150 mbar and distilled at 60 mbar (Vigreux column). The product was obtained at 85-87° C. as a colourless liquid (104 g, 62% of theory with a purity of >99% (GC)).

Workup

  1. additionwas added dropwise at 35° C., while the temperature
  2. customwas kept below 40° C
  3. extractionThe mixture was extracted twice
  4. washeach time with 500 ml of methyl tert-butyl ether, and the combined organic phases were washed twice with saturated sodium chloride solution
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated at 40° C.
  7. distillation150 mbar and distilled at 60 mbar (Vigreux column)
  8. customThe product was obtained at 85-87° C. as a colourless liquid (104 g, 62% of theory with a purity of >99% (GC))

Sources & evidence

ORD record
ord-11a8de0f40ce48c7a56391260b171c98
Source dataset
uspto-grants-2015_09
Patent number
US09145369B2

Reaction notes

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