Lithium Chloride → 3-Fluoro-4-(1,3-thiazol-4-yl)phenyl-1-ethanone

HRID 394896Notes

Reaction equation

HRID 394896 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[CH:15][S:16][CH:17]=2)=[C:9]([F:18])[CH:8]=1)(=O)=O.C([Sn](CCCC)(CCCC)[C:26]([O:28]CC)=[CH2:27])CCC.[Cl-].[Li+]>O1CCOCC1.C(OCC)(=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:18][C:9]1[CH:8]=[C:7]([C:26](=[O:28])[CH3:27])[CH:12]=[CH:11][C:10]=1[C:13]1[N:14]=[CH:15][S:16][CH:17]=1

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 223138103-Fluoro-4-(1,3-thiazol-4-yl)phenyl trifluoromethanesulfonate

Product 1

HCID 223138303-Fluoro-4-(1,3-thiazol-4-yl)phenyl-1-ethanoneYield 68%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 3-fluoro-4-(1,3-thiazol-4-yl)phenyl trifluoromethanesulfonate (1.45 g, 4.43 mmol) in dioxane (42 ml) was added tributyl(1-ethoxyvinyl)tin (1.92 g, 5.32 mmol), tetrakis(triphenylphosphine) palladium (512 mg, 0.44 mmol), lithium chloride (466 mg, 11.0 mmol), and the mixture was heated at reflux temperature for 16 hours. The reaction mixture was cooled down to room temperature, and diluted with ethyl acetate. The whole was washed with saturated potassium fluoride aqueous solution, and the precipitate was removed by filteration through celite. The resulting solution was extracted with ethyl acetate. The organic layer was concentrated in vacuo. To the residue was added THF (20 ml), 2N HCl aqueous solution (20 ml), and the mixture was heated at reflux temperature for 8 hours. The reaction mixture was cooled down to room temperature, made neutral by addition of NaHCO3, and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by flash chromatography eluting with ethyl acetate-hexane (1:5) to give title compound (666 mg, 68% yield).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux temperature for 16 hours
  3. washThe whole was washed with saturated potassium fluoride aqueous solution
  4. customthe precipitate was removed by filteration through celite
  5. extractionThe resulting solution was extracted with ethyl acetate
  6. concentrationThe organic layer was concentrated in vacuo
  7. additionTo the residue was added THF (20 ml), 2N HCl aqueous solution (20 ml)
  8. temperaturethe mixture was heated
  9. temperatureat reflux temperature for 8 hours
  10. temperatureThe reaction mixture was cooled down to room temperature
  11. additionmade neutral by addition of NaHCO3
  12. extractionextracted with ethyl acetate
  13. washThe organic layer was washed with brine
  14. dry with materialdried over MgSO4
  15. concentrationconcentrated in vacuo
  16. customThe residue was purified by flash chromatography
  17. washeluting with ethyl acetate-hexane (1:5)

Sources & evidence

ORD record
ord-2529af96fdd84807bf7f0c57ace989e9
Source dataset
uspto-grants-2003_08
Patent number
US06603008B1

Reaction notes

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