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

HRID 72696Notes

Reaction equation

HRID 72696 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>COCCOC.C(=O)([O-])[O-].[Na+].[Na+].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>[CH3:17][C:14]1[CH:15]=[CH:16][C:11]([C:6]2[N:2]([CH3:1])[N:3]=[CH:4][CH:5]=2)=[CH:12][CH:13]=1

Participants

6

Reactant 2

HCID 78054-BromotolueneHCID 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 80711,2-DimethoxyethaneSolventHCID 10340Sodium CarbonateSolvent

Procedure

A mixture of (1-methyl-1H-pyrazol-5-yl)boronic acid (C1) (60.0 g, 0.476 mol) and 1-bromo-4-methylbenzene (75.0 g, 0.438 mol) in a mixture of 1,2-dimethoxyethane (1.2 L) and 2 M aqueous sodium carbonate solution (550 mL) was degassed and purged with N2; this procedure was then repeated twice. Dichlorobis(triphenylphosphine)palladium(II) (3.1 g, 4.4 mmol) was added and the mixture was purged twice with N2. The reaction mixture was heated to reflux and stirred under N2 for 3 hours. The mixture was cooled and 1,2-dimethoxyethane was removed under reduced pressure; water (500 mL) was added to the residue, and the resulting mixture was extracted with dichloromethane (3×500 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification via silica gel chromatography (Eluent: 100:1 petroleum ether/ethyl acetate) provided the product as a yellow liquid. Yield: 55.0 g, 319 mmol, 73%. 1H NMR (400 MHz, CDCl3) δ 2.42 (s, 3H), 3.89 (s, 3H), 6.29 (d, J=1.8 Hz, 1H), 7.29 (br AB quartet, JAB=8 Hz, ΔνAB=18 Hz, 4H), 7.52 (d, J=2.0 Hz, 1H).

Workup

  1. customwas degassed
  2. custompurged with N2
  3. customthe mixture was purged twice with N2
  4. temperatureThe reaction mixture was heated
  5. temperatureto reflux
  6. temperatureThe mixture was cooled
  7. custom1,2-dimethoxyethane was removed under reduced pressure
  8. additionwater (500 mL) was added to the residue
  9. extractionthe resulting mixture was extracted with dichloromethane (3×500 mL)
  10. washThe combined organic layers were washed with saturated aqueous sodium chloride solution
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customPurification via silica gel chromatography (Eluent: 100:1 petroleum ether/ethyl acetate)

Sources & evidence

ORD record
ord-1540c7cf7f2946449aa4f303e3569758
Source dataset
uspto-grants-2014_09
Patent number
US08829010B2

Reaction notes

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