Hydrochloric Acid → Ethyl 3-(2,6-difluorophenyl)-3-oxopropanoate

HRID 449945Notes

Reaction equation

HRID 449945 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4]([OH:6])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[Cl-].[Mg+2].[Cl-].[C:27]([O:33][CH2:34][CH3:35])(=[O:32])[CH2:28]C([O-])=O.[K+].Cl>O1CCCC1.O>[F:11][C:7]1[CH:8]=[CH:9][CH:10]=[C:2]([F:1])[C:3]=1[C:4](=[O:6])[CH2:28][C:27]([O:33][CH2:34][CH3:35])=[O:32]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 97962,6-Difluorobenzoic acidHCID 682631,1'-CarbonyldiimidazoleHCID 3446434Potassium ethyl malonateHCID 5360315Magnesium Chloride

Product 1

HCID 13550002Ethyl 3-(2,6-difluorophenyl)-3-oxopropanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of 2,6-difluorobenzoic acid (15 g, 0.095 mot) and carbonyldiimidazole (18 g, 0.14 mol, 1.5 equiv) in anhydrous tetrahydrofuran (150 mL) was stirred at ambient temperature for 6 hours. In a separate flask, a suspension of anhydrous magnesium(II)chloride (9.0 g, 0.095 mol, 1.0 equiv) and potassium ethyl malonate (22 g, 0.13 mol, 1.4 equiv) in tetrahydrofuran (225 mL) was stirred at 50-60° C. for 6 hours, cooled to ambient temperature, which was then added via syringe to the solution of activated acid, and the mixture was stirred for an additional 18 hours at ambient temperature. The mixture was refluxed for 3 hours, cooled to ambient temperature, poured into water and acidified with hydrochloric acid (12 N aqueous) to pH<2. The aqueous layer was extracted with ethyl acetate and the organic extract was washed with water, dried with sodium sulfate, filtered and concentrated in vacuo, providing the titled compound.

Workup

  1. stirringwas stirred at 50-60° C. for 6 hours
  2. temperaturecooled to ambient temperature
  3. additionwhich was then added via syringe to the solution of activated acid
  4. stirringthe mixture was stirred for an additional 18 hours at ambient temperature
  5. temperatureThe mixture was refluxed for 3 hours
  6. temperaturecooled to ambient temperature
  7. extractionThe aqueous layer was extracted with ethyl acetate
  8. extractionthe organic extract
  9. washwas washed with water
  10. dry with materialdried with sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-83f9185ef1ee4d6fa384494020c519d2
Source dataset
uspto-grants-2013_07
Patent number
US08486946B2

Reaction notes

Loading…