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

HRID 1619699Notes

Reaction equation

HRID 1619699 reaction equation
[F-].[Cs+].[Cl:3][C:4]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=2)=[CH:8][C:7]([OH:17])=[C:6](I)[CH:5]=1.C([Sn](CCCC)(CCCC)[C:24]1[CH:29]=[CH:28][N:27]=[N:26][CH:25]=1)CCC>C(#N)C.C(OCC)(=O)C.[Cu](I)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:3][C:4]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=2)=[CH:8][C:7]([OH:17])=[C:6]([C:24]2[CH:29]=[CH:28][N:27]=[N:26][CH:25]=2)[CH:5]=1

Participants

8

Reactant 3

HCID 25953Cesium fluorideHCID 64097334-(Tributylstannyl)pyridazineHCID 580423086-Chloro-3'-fluoro-4-iodobiphenyl-3-ol

Product 1

HCID 1362008776-Chloro-3'-fluoro-4-(pyridazin-4-yl)biphenyl-3-olYield 85.4%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Caesium fluoride (219 mg, 1.44 mmol) was added to a solution of 6-chloro-3′-fluoro-4-iodobiphenyl-3-ol (Preparation 99, 251 mg, 0.72 mmol) and 4-(tributylstannyl)pyridazine (345 mg, 0.93 mmol) in acetonitrile (5 mL). The reaction mixture was degassed and copper iodide (28 mg, 0.15 mmol) and tetrakistriphenylphosphinepalladium (0) (83 mg, 0.07 mmol) were added. The reaction mixture was stirred at 80° C. for 3 hours. The cooled reaction mixture was diluted with ethyl acetate (20 mL) and quenched with a solution of ammonia (10%, 10 mL) and stirred for a further 10 minutes. The organic layer was separated and washed with brine (1×10 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was purified using silica gel chromatography (Biotage) eluting with heptane:ethyl acetate (93:7 to 0:100) to give the title compound (185 mg, 62%) as a yellow solid.

Workup

  1. customThe reaction mixture was degassed
  2. customThe cooled reaction mixture
  3. customquenched with a solution of ammonia (10%, 10 mL)
  4. stirringstirred for a further 10 minutes
  5. customThe organic layer was separated
  6. washwashed with brine (1×10 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified
  11. washeluting with heptane:ethyl acetate (93:7 to 0:100)

Sources & evidence

ORD record
ord-b9c241deedde462cbf745ecbe0469d05
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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