Potassium Phosphate, Tribasic → 5-[2-(benzyloxy)-5-(trifluoromethoxy)phenyl]-1-methyl-1H-pyrazole

HRID 46346Notes

Reaction equation

HRID 46346 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][C:10]=1Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:21][N:22]1[C:26](B(O)O)=[CH:25][CH:24]=[N:23]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1(/C=C/C(=O)/C=C/C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][C:10]=1[C:26]1[N:22]([CH3:21])[N:23]=[CH:24][CH:25]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 11182610(1-methyl-1H-pyrazol-5-yl)boronic acidHCID 112909662-Benzyloxy-5-(trifluoromethoxy)bromobenzene

Product 1

HCID 594365685-[2-(benzyloxy)-5-(trifluoromethoxy)phenyl]-1-methyl-1H-pyrazoleYield 70%

Reagents, catalysts & solvents 3

HCID 15673654(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 1-(benzyloxy)-2-bromo-4-(trifluoromethoxy)benzene (Preparation 535, 3.3 g, 9.5 mmol) and (1-methyl-1H-pyrazol-5-yl)boronic acid (Preparation 403, 1.2 g, 9.5 mmol) 1,4-in dioxane (25 mL) was degassed under argon for 30 minutes. Under argon, (1E,4E)-1,5-Diphenylpenta-1,4-dien-3-one-palladium (3:2) (348 mg, 0.38 mmol) and tricyclohexylphosphine (213 mg, 0.76 mmol) were added followed by the dropwise addition of a degassed solution of tripotassium phosphate (4 g, 19 mmol) in water (12.6 mL). Reaction mixture was refluxed for 16 hours before cooling to room temperature and filtering through Celite™. The filtrate was concentrated in vacuo and the residue was diluted with ethyl acetate (100 mL). The organic extract was washed with water, saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. Purification by silica gel column chromatography eluting with ethyl acetate:hexane (1:9, by volume) afforded the title compound, 2.3 g, 70% yield.

Workup

  1. customReaction mixture
  2. temperaturewas refluxed for 16 hours
  3. filtrationfiltering through Celite™
  4. concentrationThe filtrate was concentrated in vacuo
  5. additionthe residue was diluted with ethyl acetate (100 mL)
  6. extractionThe organic extract
  7. washwas washed with water, saturated aqueous sodium chloride solution
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customPurification by silica gel column chromatography
  11. washeluting with ethyl acetate:hexane (1:9, by volume)

Sources & evidence

ORD record
ord-d82df57993f04b6e95312e4f1c2b1f8b
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Reaction notes

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