Potassium Phosphate, Tribasic → 3-bromo-5-(2-chloro-4-fluorophenyl)-1-methyl-1H-pyrazole

HRID 2276024Notes

Reaction equation

HRID 2276024 reaction equation
[Br:1][C:2]1[CH:6]=[C:5](Br)[N:4]([CH3:8])[N:3]=1.[Cl:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C(OCC)(=O)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>[Br:1][C:2]1[CH:6]=[C:5]([C:11]2[CH:12]=[CH:13][C:14]([F:16])=[CH:15][C:10]=2[Cl:9])[N:4]([CH3:8])[N:3]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 177502292-Chloro-4-fluorobenzeneboronic acidHCID 666141313,5-dibromo-1-methyl-1H-pyrazole2×

Product 1

HCID 666135773-bromo-5-(2-chloro-4-fluorophenyl)-1-methyl-1H-pyrazole

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 3,5-dibromo-1-methyl-1H-pyrazole (i.e. the product of Step B) (2.00 g, 8.33 mmol) in toluene (40 mL) was sparged with a stream of argon for 45 minutes, and then 2-chloro-4-fluorophenylboronic acid (1.59 g, 9.11 mmol), potassium phosphate tribasic (5.30 g, 25.0 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.48 g, 0.41 mmol) were added. The reaction mixture was heated at 90° C. for 3 h, and then cooled to room temperature and diluted with ethyl acetate (250 mL). The mixture was washed with water (25 mL) and saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography (5 to 40% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a white solid (620 mg).

Workup

  1. customwas sparged with a stream of argon for 45 minutes
  2. temperaturecooled to room temperature
  3. washThe mixture was washed with water (25 mL) and saturated aqueous sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting material was purified by silica gel chromatography (5 to 40% gradient of ethyl acetate in hexanes as eluant)

Sources & evidence

ORD record
ord-fe14d3cb4d5443ab8d92bc857947f69b
Source dataset
uspto-grants-2015_09
Patent number
US09131693B2

Reaction notes

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