Ethanol → 3-(1-Methyl-1H-pyrazol-4-yl)aniline

HRID 419320Notes

Reaction equation

HRID 419320 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[CH3:9][CH2:10]O.C([O-])([O-])=O.[Na+].[Na+].CC1(C)C(C)(C)OBO1.[NH:27]1[CH:31]=C[CH:29]=[N:28]1>C1(C)C=CC=CC=1.O.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.CCOC(C)=O>[CH3:29][N:28]1[CH:10]=[C:9]([C:2]2[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=2)[NH2:5])[CH:31]=[N:27]1

Participants

9

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 115623-BromoanilineHCID 178431122HCID 178431122, compound

Product 1

HCID 288753303-(1-Methyl-1H-pyrazol-4-yl)anilineYield 51%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Bromoaniline (0.50 mL, 4.6 mmol) was dissolved in 30 mL of PhMe with stirring, and 15 mL of EtOH was added. Na2CO3 (3.06 g, 28.9 mmol) in 15 mL of H2O was added followed by 1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-1H-pyrazole (0.955 g, 4.59 mmol). Pd(PPh3)4 (0.265 g, 0.229 mmol) was added, and the mixture was heated to reflux with stirring overnight. The mixture was cooled to rt and poured into EtOAc and H2O. The mixture was filtered through celite, and the layers were separated. The organic layer was washed with brine. The organic layer was concentrated and purified by flash chromatography to afford 0.408 g (51%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 7.92 (s, 1H), 7.65 (s, 1H), 6.96 (t, J=7.7 Hz, 1H), 6.71-6.64 (m, 2H), 6.41-6.36 (m, 1H), 4.99 (br s, 2H), 3.82 (s, 3H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux
  3. stirringwith stirring overnight
  4. filtrationThe mixture was filtered through celite
  5. customthe layers were separated
  6. washThe organic layer was washed with brine
  7. concentrationThe organic layer was concentrated
  8. custompurified by flash chromatography

Sources & evidence

ORD record
ord-3f0014354957416fac62ab3329beaec3
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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