Cesium fluoride → 6-Chloro-4'-fluoro-4-(pyridazin-4-yl)biphenyl-3-ol

HRID 1619703Notes

Reaction equation

HRID 1619703 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[CH:6][C:5]([OH:15])=[C:4](I)[CH:3]=1.C([Sn](CCCC)(CCCC)[C:22]1[CH:27]=[CH:26][N:25]=[N:24][CH:23]=1)CCC.[F-].[Cs+]>C(#N)C.[Cu]I.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[CH:6][C:5]([OH:15])=[C:4]([C:22]2[CH:27]=[CH:26][N:25]=[N:24][CH:23]=2)[CH:3]=1

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 64097334-(Tributylstannyl)pyridazineHCID 580423526-Chloro-4'-fluoro-4-iodobiphenyl-3-ol

Product 1

HCID 1362008786-Chloro-4'-fluoro-4-(pyridazin-4-yl)biphenyl-3-olYield 58%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
45 °C

Procedure

A suspension of 6-chloro-4′-fluoro-4-iodobiphenyl-3-ol (Preparation 103, 300 mg, 0.86 mmol), 4-(tributylstannyl)-pyridazine (413 mg, 1.12 mmol), caesium fluoride (261 mg, 1.72 mmol), and copper (I) iodide (33 mg, 0.17 mmol) in acetonitrile (5 mL) was degassed for 20 minutes under nitrogen. Tetrakistriphenylphosphinepalladium (0) (100 mg, 0.09 mmol) was added and the reaction mixture was heated for 18 hours at 45° C. under nitrogen. The cooled reaction mixture was filtered through Arbocel and the Arbocel pad was washed with ethyl acetate (100 mL). The organic layer was washed with brine (2×15 mL), dried over MgSO4, filtered and evaporated. The residue was purified by silica gel chromatography eluting with 20% heptane in ethyl acetate to afford the title compound (150 mg, 58%) as an oil.

Workup

  1. customwas degassed for 20 minutes under nitrogen
  2. customThe cooled reaction mixture
  3. filtrationwas filtered through Arbocel
  4. washthe Arbocel pad was washed with ethyl acetate (100 mL)
  5. washThe organic layer was washed with brine (2×15 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with 20% heptane in ethyl acetate

Sources & evidence

ORD record
ord-9ee11bb48fe04983a7c803ad7b46bea2
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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