4-Bromotoluene → 1-Methyl-5-(4-methylphenyl)-1H-pyrazole

HRID 1907173Notes

Reaction equation

HRID 1907173 reaction equation
[CH3:1][N:2]1[C:6](B(O)O)=[CH:5][CH:4]=[N:3]1.Br[C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.COCCOC.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>[CH3:1][N:2]1[C:6]([C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=2)=[CH:5][CH:4]=[N:3]1

Participants

7

Reactant 3

HCID 78054-BromotolueneHCID 10340Sodium CarbonateHCID 11182610(1-methyl-1H-pyrazol-5-yl)boronic acid

Product 1

HCID 125810901-Methyl-5-(4-methylphenyl)-1H-pyrazole

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

(1-Methyl-1H-pyrazol-5-yl)boronic acid (2.0 g, 16 mmol), 1-bromo-4-methylbenzene (1.96 mL, 15.9 mmol), sodium carbonate (5.05 g, 47.6 mmol) and dichlorobis(triphenylphosphine)palladium(II) (557 mg, 0.794 mmol) were combined in a mixture of water (20 mL) and 1,2-dimethoxyethane (100 mL), and heated at 80° C. for 18 hours. After the reaction mixture had cooled, it was filtered through Celite, and concentrated in vacuo. The residue was partitioned between water and ethyl acetate, and the aqueous layer was extracted with additional ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure. Chromatography on silica gel (Gradient: 0% to 50% ethyl acetate in heptane) provided the product as a yellow oil. Yield: 1.15 g, 6.68 mmol, 42%. LCMS m/z 173.1 (M+1). 1H NMR (400 MHz, CDCl3) δ 2.42 (s, 3H), 3.89 (s, 3H), 6.29 (d, J=2.0 Hz, 1H), 7.30 (br AB quartet, JAB=8 Hz, ΔvAB=18 Hz, 4H), 7.51 (d, J=1.9 Hz, 1H).

Workup

  1. temperatureAfter the reaction mixture had cooled
  2. filtrationit was filtered through Celite
  3. concentrationconcentrated in vacuo
  4. customThe residue was partitioned between water and ethyl acetate
  5. extractionthe aqueous layer was extracted with additional ethyl acetate
  6. dry with materialThe combined organic layers were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-48e6ac56f7f74608bb1e00692fc6c36f
Source dataset
uspto-grants-2013_12
Patent number
US08598155B2

Reaction notes

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