2,4-Difluorophenylacetonitrile → 3-(2,4-difluorophenyl)-6-trifluoromethyl-2H-pyran-2-one

HRID 1385920Notes

Reaction equation

HRID 1385920 reaction equation
CC(C)([O-:4])C.[K+].[F:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[CH2:15][C:16]#N.C(O/[CH:21]=[CH:22]/[C:23](=[O:28])[C:24]([F:27])([F:26])[F:25])C>C1COCC1>[F:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[C:15]1[C:16](=[O:4])[O:28][C:23]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 695652,4-DifluorophenylacetonitrileHCID 5709222(3E)-4-Ethoxy-1,1,1-trifluoro-3-buten-2-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 154571853-(2,4-difluorophenyl)-6-trifluoromethyl-2H-pyran-2-oneYield 76.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

7.7 g (69 mmol) of potassium tert-butoxide was dissolved in 200 ml of THF, and 10 g (65 mmol) of 2,4-difluorophenyl acetonitrile was dropwise added thereto under cooling with ice. Ten minutes later, 13.5 g (69 immol) of (E)-4-ethoxy-1,1,1-trifluoro-3-buten-2-one was dropwise added thereto, followed by stirring at room temperature for 4 hours. THF was distilled off under reduced pressure. Then, the obtained residue was poured into water, acidified to pH 1 with 1N hydrochloric acid and then extracted with ethyl acetate. After washing with water and an aqueous sodium hydrogencarbonate solution, the organic layer was dried over anhydrous magnesium sulfate. And then, the ethyl acetate was distilled off under reduced pressure. To the obtained residue, 150 ml of concentrated hydrochloric acid was added, followed by stirring for 4 hours under heating and refluxing. This reaction solution was poured into ice water and extracted with ethyl acetate, followed by washing with water. The organic layer was dried over anhydrous magnesium sulfate, and then, ethyl acetate was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 13.8 g (yield: 76%) of the desired product. Melting point: 98-100° C. 1H-NMR (400 MHz, CDCl3) δ value: 6.78(1H,d), 6.95(2H,m), 7.52(1H,d), 7.56(1H,q)ppm.

Workup

  1. temperatureunder cooling with ice
  2. distillationTHF was distilled off under reduced pressure
  3. additionThen, the obtained residue was poured into water
  4. extractionextracted with ethyl acetate
  5. washAfter washing with water
  6. dry with materialan aqueous sodium hydrogencarbonate solution, the organic layer was dried over anhydrous magnesium sulfate
  7. distillationAnd then, the ethyl acetate was distilled off under reduced pressure
  8. additionTo the obtained residue, 150 ml of concentrated hydrochloric acid was added
  9. stirringby stirring for 4 hours
  10. temperatureunder heating
  11. temperaturerefluxing
  12. additionThis reaction solution was poured into ice water
  13. extractionextracted with ethyl acetate
  14. washby washing with water
  15. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  16. distillationethyl acetate was distilled off under reduced pressure
  17. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-2ffa3ae5fcd64e119b335e59bfa8240f
Source dataset
uspto-grants-2001_07
Patent number
US06265349B1

Reaction notes

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