Cesium fluoride → 5-Fluoro-2-pyridazin-4-yl-4-(trifluoromethyl)phenol

HRID 2283627Notes

Reaction equation

HRID 2283627 reaction equation
[F-].[Cs+].[F:3][C:4]1[C:5]([C:12]([F:15])([F:14])[F:13])=[CH:6][C:7](I)=[C:8]([OH:10])[CH:9]=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:5]([C:12]([F:15])([F:14])[F:13])=[CH:6][C:7]([C:21]2[CH:26]=[CH:25][N:24]=[N:23][CH:22]=2)=[C:8]([OH:10])[CH:9]=1

Participants

9

Reactant 3

HCID 25953Cesium fluorideHCID 64097334-(Tributylstannyl)pyridazineHCID 594364965-Fluoro-2-iodo-4-(trifluoromethyl)phenol

Product 1

HCID 1360636295-Fluoro-2-pyridazin-4-yl-4-(trifluoromethyl)phenolYield 62.5%

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 (570 mg, 3.8 mmol), tetrakis(triphenylphosphine)palladium(0) (220 mg, 0.19 mmol), and copper(I) iodide (72 mg, 0.38 mmol) were added to a solution of 5-fluoro-2-iodo-4-(trifluoromethyl)phenol (Preparation 8, 579 mg, 1.89 mmol) and 4-(tributylstannyl)pyridazine (770 mg, 2.1 mmol) in N,N-dimethylformamide (4 mL). The reaction mixture was heated at 45° C. under an atmosphere of argon. After 1.5 hours, the reaction mixture was cooled to ambient temperature, diluted with ethyl acetate and water, and filtered through diatomaceous earth. The layers were separated, and the organic layer was washed with water, aqueous lithium chloride, and brine. The organic layer was 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 a tan solid (305 mg).

Workup

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

Sources & evidence

ORD record
ord-06f8ce1312e64b94ba26acfd0636d15d
Source dataset
uspto-grants-2015_09
Patent number
US09145407B2

Reaction notes

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