2,4-Difluorophenol → HCID 178505881, compound

HRID 271077Notes

Reaction equation

HRID 271077 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[OH:9].CC(C)([O-])C.[K+].Cl[C:17]1[N:22]=[C:21]2[NH:23][N:24]=[C:25]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[Cl:32])[C:20]2=[CH:19][CH:18]=1>>[Cl:32][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[C:25]1[C:20]2[C:21](=[N:22][C:17]([O:9][C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])=[CH:18][CH:19]=2)[NH:23][N:24]=1

Participants

4

Reactant 3

HCID 1230512,4-DifluorophenolHCID 23665647Potassium tert-butoxideHCID 178477865HCID 178477865, compound

Product 1

HCID 178505881HCID 178505881, compoundYield 16.4%

Conditions

Temperature
0 °C

Procedure

2,4-Difluorophenol (517 mg, 4 mmol) was placed in a 10 mL microwave reactor tube under nitrogen and cooled in an ice bath. Potassium t-butoxide (4 mL of 1.0 M solution in THF) was added dropwise, and the solution was stirred for five minutes at 0° C. The reaction mixture was warmed to room temperature, and 6-chloro-3-(2-chloro-phenyl)-1H-pyrazolo[3,4-b]pyridine (350 mg, 1.33 mmol) was added in one portion. The reaction was then heated to 160° C. via microwave for nine hours. The reaction mixture was cooled and partitioned between water and ethyl acetate. The organic phase was washed with brine, followed by water, and then dried over MgSO4. The solvent was removed under reduced pressure, and the residue was eluted through a FLASH column using 0.5% MeOH in methylene chloride. Solvent was removed, and the residue was recrystallized from methylene chloride/hexanes to afford 78 mg of 3-(2-Chloro-phenyl)-6-(2,4-difluoro-phenoxy)-1H-pyrazolo[3,4-b]pyridine as a white solid. Mass Spec. M+H=358.

Workup

  1. temperaturecooled in an ice bath
  2. temperatureThe reaction mixture was warmed to room temperature
  3. temperatureThe reaction was then heated to 160° C. via microwave for nine hours
  4. temperatureThe reaction mixture was cooled
  5. custompartitioned between water and ethyl acetate
  6. washThe organic phase was washed with brine
  7. dry with materialdried over MgSO4
  8. customThe solvent was removed under reduced pressure
  9. washthe residue was eluted through a FLASH column
  10. customSolvent was removed
  11. customthe residue was recrystallized from methylene chloride/hexanes

Sources & evidence

ORD record
ord-5dc31c1d592548809b25afe66afb18b9
Source dataset
uspto-grants-2008_11
Patent number
US07452880B2

Reaction notes

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