Sulfuric Acid → Ethyl 4,4-difluoroacetoacetate

HRID 1618086Notes

Reaction equation

HRID 1618086 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 nitrogen, 46.7 g (1.168 mol) of sodium hydride (60% dispersion in paraffin) were added to 600 ml of tetrahydrofuran. At 35° C. a mixture of 125 g (1.008 mol) of difluoroethyl acetate and 88.7 g (1.010 mol) of ethyl acetate was added dropwise while the temperature was maintained at below 40° C. This was followed by further stirring at room temperature overnight. The reaction mixture was carefully poured into 1.7 L of ice-water and adjusted to pH 3 with sulphuric acid. The reaction mixture was extracted twice with 500 ml of methyl tert-butyl ether each time, the combined organic phases were washed twice with saturated sodium chloride solution, dried over sodium sulphate and concentrated at 40° C. and 150 mbar before distillation at 60 mbar (Vigreux column). The product was obtained at 85-87° C. as a colourless liquid (104 g, 62% of theory having a purity of >99% (GC)).

Workup

  1. additionwas added dropwise while the temperature
  2. temperaturewas maintained at below 40° C
  3. extractionThe reaction mixture was extracted twice with 500 ml of methyl tert-butyl ether each time
  4. washthe 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 before distillation at 60 mbar (Vigreux column)
  8. customThe product was obtained at 85-87° C. as a colourless liquid (104 g, 62% of theory

Sources & evidence

ORD record
ord-bbdb639f8dff418295bb231d66c315d8
Source dataset
uspto-grants-2014_07
Patent number
US08765971B2

Reaction notes

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