Cesium fluoride → Ethyl 2-pyridazin-4-yl-4-(trifluoromethyl)benzoate

HRID 509116Notes

Reaction equation

HRID 509116 reaction equation
[CH2:1]([O:3][C:4](=[O:16])[C:5]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][C:6]=1I)[CH3:2].C([Sn](CCCC)(CCCC)[C:22]1[CH:27]=[CH:26][N:25]=[N:24][CH:23]=1)CCC.[F-].[Cs+]>C(#N)C.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)I>[N:24]1[CH:23]=[CH:22][C:27]([C:6]2[CH:7]=[C:8]([C:11]([F:14])([F:13])[F:12])[CH:9]=[CH:10][C:5]=2[C:4]([O:3][CH2:1][CH3:2])=[O:16])=[CH:26][N:25]=1

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 64097334-(Tributylstannyl)pyridazineHCID 18431635Ethyl 2-iodo-4-(trifluoromethyl)benzoate

Product 1

HCID 68042663Ethyl 2-pyridazin-4-yl-4-(trifluoromethyl)benzoateYield 81.3%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 2-iodo-4-trifluoromethylbenzoic acid ethyl ester (200 mg, 0.581 mmol) in acetonitrile (5 mL) was added 4-(tributylstannyl)pyridazine (214 mg, 0.581 mmol) and caesium fluoride (176 mg, 1.16 mmol). The solution was sparged with nitrogen before the addition of tetrakis(triphenylphosphine)palladium (0) (26 mg, 0.023 mmol) and copper iodide (22 mg, 0.116 mmol). The reaction mixture was sparged with nitrogen then heated at 45° C. for 2 hours. The reaction mixture was cooled to ambient temperature, diluted with ethyl acetate and filtered through Celite™. An aqueous solution of potassium fluoride was added and the reaction mixture was stirred for 16 hours. The organic layer was separated, washed with water, followed by a saturated aqueous solution of sodium chloride. The organic layer was dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The material was purified by column chromatography (100-200 silica, eluting with 60% ethyl acetate in heptane). Fractions containing product were combined and concentrated in vacuo to obtain the title compound as a solid (140 mg).

Workup

  1. customThe reaction mixture was sparged with nitrogen
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. additiondiluted with ethyl acetate
  4. filtrationfiltered through Celite™
  5. additionAn aqueous solution of potassium fluoride was added
  6. customThe organic layer was separated
  7. washwashed with water
  8. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe material was purified by column chromatography (100-200 silica, eluting with 60% ethyl acetate in heptane)
  12. additionFractions containing product
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7ebd34c6cb764847ad3dc7c626ef72c3
Source dataset
uspto-grants-2015_08
Patent number
US09096558B2

Reaction notes

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