Cesium fluoride → 2-(Pyridazin-4-yl)-4-(trifluoromethyl)phenol

HRID 2359316Notes

Reaction equation

HRID 2359316 reaction equation
[F-].[Cs+].C([Sn](CCCC)(CCCC)[C:8]1[CH:13]=[CH:12][N:11]=[N:10][CH:9]=1)CCC.[F:22][C:23]([F:33])([F:32])[C:24]1[CH:29]=[C:28](I)[C:27]([OH:31])=[CH:26][CH:25]=1>[Cu]I.C(#N)C>[N:11]1[CH:12]=[CH:13][C:8]([C:26]2[CH:25]=[C:24]([C:23]([F:33])([F:32])[F:22])[CH:29]=[CH:28][C:27]=2[OH:31])=[CH:9][N:10]=1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 64097334-(Tributylstannyl)pyridazineHCID 115728162-Iodo-4-(trifluoromethyl)phenol

Product 1

HCID 1357416972-(Pyridazin-4-yl)-4-(trifluoromethyl)phenolYield 76.5%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
47.5 °C

Procedure

To a 5 L jacketed vessel was added acetonitrile (9 L) and the solvent was sparged with nitrogen for 2 hours. To the solvent was added cesium fluoride (335.8 g, 2.21 moles), 4-(tributylstannyl)pyridazine (408 g, 1.11 moles), 4-trifluoromethyl-6-iodophenol (318.33 g, 1.11 moles), palladium tetrakis triphenylphosphine (61.31 g, 53.05 mmole) and copper (I) iodide (40 g, 210 mmol) at 20° C. The resulting orange suspension was heated to 45-50° C. for 2 hours. The reaction was cooled and partitioned between ter-tbutylmethylether (2×5 L) and 2N (aq) HCl (2×5 L). The resulting biphasic solution was filtered and the layers separated. The aqueous phases were combined and basified with 4M (aq) sodium hydroxide solution (6 L) to obtain a pH=4-5. The resulting suspension was extracted into ethyl acetate (10 L) and the organic layer concentrated to dryness to afford the title compound (204 g, 60%) as an orange solid.

Workup

  1. customthe solvent was sparged with nitrogen for 2 hours
  2. temperatureThe reaction was cooled
  3. custompartitioned between ter-tbutylmethylether (2×5 L) and 2N (aq) HCl (2×5 L)
  4. filtrationThe resulting biphasic solution was filtered
  5. customthe layers separated
  6. customto obtain a pH=4-5
  7. extractionThe resulting suspension was extracted into ethyl acetate (10 L)
  8. concentrationthe organic layer concentrated to dryness

Sources & evidence

ORD record
ord-1d3d06066df84f1d89f5023212b84c8a
Source dataset
uspto-grants-2014_04
Patent number
US08685977B2

Reaction notes

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