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

HRID 406594Notes

Reaction equation

HRID 406594 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 666141311H-Pyrazole, 3,5-dibromo-1-methyl-2×

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-8624a151838f4200b05e2ca0b859e5e5
Source dataset
uspto-grants-2014_06
Patent number
US08754115B2

Reaction notes

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