Cesium fluoride → HCID 136365476, compound

HRID 2283629Notes

Reaction equation

HRID 2283629 reaction equation
[F-].[Cs+].[F:3][C:4]1[C:9]([C:10]([F:13])([F:12])[F:11])=[CH:8][C:7]([OH:14])=[C:6](I)[CH:5]=1.C([Sn](CCCC)(CCCC)[C:21]1[CH:26]=[CH:25][N:24]=[N:23][CH:22]=1)CCC>CN(C)C=O.C(OCC)(=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[F:3][C:4]1[C:9]([C:10]([F:13])([F:12])[F:11])=[CH:8][C:7]([OH:14])=[C:6]([C:21]2[CH:26]=[CH:25][N:24]=[N:23][CH:22]=2)[CH:5]=1

Participants

9

Reactant 3

HCID 25953Cesium fluorideHCID 64097334-(Tributylstannyl)pyridazineHCID 66652905HCID 66652905, compound

Product 1

HCID 136365476HCID 136365476, compoundYield 89.1%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

Cesium fluoride (790 mg, 5.2 mmol), tetrakis(triphenylphosphine)palladium(0) (300 mg, 0.26 mmol), and copper(I) iodide (100 mg, 0.52 mmol) were added to a solution of 4-fluoro-2-iodo-5-(trifluoromethyl)phenol (Preparation 10, 800 mg, 2.6 mmol) and 4-(tributylstannyl)pyridazine (1.1 g, 2.9 mmol) in N,N-dimethylformamide (6 mL). The reaction mixture was heated at 45° C. under an atmosphere of argon. After 1 hour, the reaction mixture was cooled to ambient temperature, diluted with ethyl acetate and water, and filtered through diatomaceous earth. The solids were washed with additional ethyl acetate. The layers were separated, and the organic layer washed with water, aqueous lithium chloride and brine, then dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was taken up in dichloromethane, concentrated onto diatomaceous earth, and purified by automated silica gel flash chromatography (100% dichloromethane to 10% methanol in dichloromethane gradient elution) to afford the title compound as an orange solid (598 mg).

Workup

  1. temperaturethe reaction mixture was cooled to ambient temperature
  2. filtrationfiltered through diatomaceous earth
  3. washThe solids were washed with additional ethyl acetate
  4. customThe layers were separated
  5. washthe organic layer washed with water, aqueous lithium chloride and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. concentrationconcentrated onto diatomaceous earth
  10. custompurified by automated silica gel flash chromatography (100% dichloromethane to 10% methanol in dichloromethane gradient elution)

Sources & evidence

ORD record
ord-244c5bc0e98d46fb8ba0dc7f66c78984
Source dataset
uspto-grants-2015_09
Patent number
US09145407B2

Reaction notes

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