Water → 4-[[4-(2-Chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3,5-difluorobenzonitrile

HRID 514233Notes

Reaction equation

HRID 514233 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([F:19])[C:9]=1[O:10][C:11]1[N:15]([CH3:16])[N:14]=[C:13]([CH3:17])[C:12]=1I)[C:5]#[N:6].[Cl:20][C:21]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:20][C:21]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=1[C:12]1[C:13]([CH3:17])=[N:14][N:15]([CH3:16])[C:11]=1[O:10][C:9]1[C:2]([F:1])=[CH:3][C:4]([C:5]#[N:6])=[CH:7][C:8]=1[F:19]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 177502292-Chloro-4-fluorobenzeneboronic acid2×HCID 666121553,5-Difluoro-4-[(4-iodo-1,3-dimethyl-1H-pyrazol-5-yl)oxy]benzonitrile2×

Product 1

HCID 666135214-[[4-(2-Chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3,5-difluorobenzonitrile

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 3,5-difluoro-4-[(4-iodo-1,3-dimethyl-1H-pyrazol-5-yl)oxy]-benzonitrile (i.e. the product of Step B) (1.0 g, 2.67 mmol) in 1,4-dioxane (6 mL) was added 2-chloro-4-fluorobenzeneboronic acid (alternatively named B-(2-chloro-4-fluorophenyl)-boronic acid) (0.93 g, 5.33 mmol), dichloro(bis)triphenylphosphine palladium(II) (alternatively named bis(triphenylphosphine)palladium(II) dichloride) (93 mg, 0.13 mmol), potassium carbonate (0.74 g, 5.33 mmol), and water (4 mL). The resulting mixture was heated at reflux for 5 h, allowed to cool, and partitioned between water (20 mL) and ethyl acetate (20 mL). The organic layer was dried over MgSO4 and concentrated. The residue was purified by chromatography on silica gel with a gradient of hexanes/ethyl acetate to obtain the title compound as an off-white solid (110 mg).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 5 h
  3. temperatureto cool
  4. custompartitioned between water (20 mL) and ethyl acetate (20 mL)
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography on silica gel with a gradient of hexanes/ethyl acetate

Sources & evidence

ORD record
ord-4550cc4f5ac64b80a47933a281741825
Source dataset
uspto-grants-2015_08
Patent number
US09107412B2

Reaction notes

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