Triphenylphosphine Oxide → HCID 136200884, compound

HRID 1619669Notes

Reaction equation

HRID 1619669 reaction equation
I[C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[N:10][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:12][CH:13]=2)[CH:5]=[CH:4][C:3]=1[OH:18].C([Sn](CCCC)(CCCC)[C:24]1[CH:29]=[CH:28][N:27]=[N:26][CH:25]=1)CCC.[F-].[Cs+].C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(#N)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]>[N:26]1[CH:25]=[CH:24][C:29]([C:2]2[CH:7]=[C:6]([C:8]3[CH:9]=[N:10][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:12][CH:13]=3)[CH:5]=[CH:4][C:3]=2[OH:18])=[CH:28][N:27]=1

Participants

8

Reactant 4

HCID 13097Triphenylphosphine OxideHCID 25953Cesium fluorideHCID 64097334-(Tributylstannyl)pyridazineHCID 580423402-Iodo-4-(6-(trifluoromethyl)pyridin-3-yl)phenol

Product 1

HCID 136200884HCID 136200884, compound

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

2-Iodo-4-(6-(trifluoromethyl)pyridin-3-yl)phenol (Preparation 60, 840 mg, 2.30 mmol) was dissolved in acetonitrile (20 mL) and 4-(tributylstannyl)pyridazine (1.10 g, 2.99 mmol), caesium fluoride (698 mg, 4.60 mmol), copper iodide (87 mg, 0.46 mmol) and tetrakis(triphenylphosphine)palladium (0) (266 mg, 0.23 mmol) were added. The reaction mixture was stirred at 80° C. for 18 hours and then partitioned between ethyl acetate and water containing 0.88 ammonia. The resulting mixture was stirred for 15 minutes and then filtered through a pad of celite. The aqueous phase was separated and extracted with ethyl acetate (2×20 mL) and the combined organic phases were washed with brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was purified on silica gel by Biotage (10% to 100% EtOAc in heptane over 25 CV) to give a mixture of the title compound and triphenylphosphine oxide. The residue was triturated with dichloromethane to give the title compound (360 mg, 50%) as a white solid.

Workup

  1. custompartitioned between ethyl acetate and water containing 0.88 ammonia
  2. stirringThe resulting mixture was stirred for 15 minutes
  3. filtrationfiltered through a pad of celite
  4. customThe aqueous phase was separated
  5. extractionextracted with ethyl acetate (2×20 mL)
  6. washthe combined organic phases were washed with brine
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified on silica gel by Biotage (10% to 100% EtOAc in heptane over 25 CV)
  11. customto give

Sources & evidence

ORD record
ord-2db79a1e469a4cc298b616b0ee2928f1
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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