Acetic Anhydride → Butanoic acid, 2-(ethoxymethylene)-4,4-difluoro-3-oxo-, ethyl ester

HRID 222777Notes

Reaction equation

HRID 222777 reaction equation
[C:1]([O:4][C:5](=O)C)(=O)[CH3:2].[F:8][CH:9]([F:18])[C:10](=[O:17])[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13].C(OCC)(OCC)OCC.FC(F)C(OCC)=O>C(O)C.C(OCC)(=O)C>[CH2:1]([O:4][CH:5]=[C:11]([C:10](=[O:17])[CH:9]([F:18])[F:8])[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH3:2]

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 9961Ethyl difluoroacetateHCID 31214Ethyl orthoformateHCID 67697Ethyl 4,4-difluoroacetoacetate2×

Product 1

HCID 53395411Butanoic acid, 2-(ethoxymethylene)-4,4-difluoro-3-oxo-, ethyl ester

Reagents, catalysts & solvents 1

HCID 21584252Ethanol ethylacetateSolvent

Conditions

Temperature
110 °C

Procedure

365.2 g of acetic anhydride (3.54 mol) were initially charged in the stirred vessel and heated to 110° C. Within 2 hours, 356.3 g of crude ethyl 4,4-difluoroacetoacetate from synthesis example 7 (26.5% ethyl 4,4-difluoroacetoacetate solution in ethanol/ethyl acetate) and 154.4 g (1.02 mol) of triethyl orthoformate were metered in in parallel. After about half had been fed in, reflux set in at 106° C. At the end of the metered addition, the internal temperature was 92° C. The mixture was stirred for a further 5 hours at reflux temperature and then cooled to 25° C. At a pressure of 150 mbar, the low boilers (ethyl acetate, acetic acid, acetic anhydride, triethyl orthoformate) were distilled off at internal temperature from 40-90° C. To complete the removal, the pressure is lowered to 5 mbar at 90° C., and the distillation bottoms are then stirred at 95° C./5 mbar for 1 hour. The resulting distillation residue (127.5 g) comprised 90.7% by weight of the desired ethyl 2-ethoxymethylene-4,4-difluoro-3-oxobutyrate. This corresponds to an overall yield over the two synthesis stages of 86.6% (based on the ethyl difluoroacetate used in working example 7).

Workup

  1. temperaturereflux
  2. customset in at 106° C
  3. additionAt the end of the metered addition
  4. customwas 92° C
  5. temperatureat reflux temperature
  6. temperaturecooled to 25° C
  7. distillationAt a pressure of 150 mbar, the low boilers (ethyl acetate, acetic acid, acetic anhydride, triethyl orthoformate) were distilled off at internal temperature from 40-90° C
  8. customthe removal
  9. customis lowered to 5 mbar at 90° C.
  10. distillationthe distillation
  11. stirringbottoms are then stirred at 95° C./5 mbar for 1 hour
  12. distillationThe resulting distillation residue (127.5 g)
  13. customThis corresponds to an overall yield over the two synthesis stages of 86.6% (

Sources & evidence

ORD record
ord-b9e116ce6e9b4a73bd84d751e246c866
Source dataset
uspto-grants-2012_06
Patent number
US08207354B2

Reaction notes

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