Potassium Carbonate → t-Butyl 2-(5-methylpyrazin-2-yl)-1H-pyrrole-1-carboxylate

HRID 1964515Notes

Reaction equation

HRID 1964515 reaction equation
Br[C:2]1[CH:7]=[N:6][C:5]([CH3:8])=[CH:4][N:3]=1.[C:9]([O:13][C:14]([N:16]1[CH:20]=[CH:19][CH:18]=[C:17]1B(O)O)=[O:15])([CH3:12])([CH3:11])[CH3:10].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O>[CH3:8][C:5]1[N:6]=[CH:7][C:2]([C:17]2[N:16]([C:14]([O:13][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:15])[CH:20]=[CH:19][CH:18]=2)=[N:3][CH:4]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 27343211-(tert-Butoxycarbonyl)-2-pyrroleboronic AcidHCID 224193462-Bromo-5-methylpyrazine

Product 1

HCID 66681439t-Butyl 2-(5-methylpyrazin-2-yl)-1H-pyrrole-1-carboxylateYield 96%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Commercially available 2-bromo-5-methylpyrazine (260 mg, 1.50 mmol) and commercially available 1-(t-butoxycarbonyl)pyrrole-2-boronic acid (380 mg, 1.80 mmol) were dissolved in 1,2-dimethoxyethane (20 mL), and palladium (II) acetate (17.0 mg, 0.076 mmol), triphenylphosphine (79.0 mg, 0.301 mmol) and an aqueous potassium carbonate solution (1.5M, 2.0 mL, 3.00 mmol) were added, followed by stirring at 100° C. for 19 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, water (20 mL) and ethyl acetate (20 mL) were added, and the solution was separated. The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=5%-30%) to afford the desired compound (373 mg, yield 96%) as a yellow oil.

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. customthe solution was separated
  3. washThe organic layer was washed with saturated brine
  4. dry with materialsubsequently dried over anhydrous magnesium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe resulting residue was purified
  7. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=5%-30%)

Sources & evidence

ORD record
ord-b97bf438ba8348c39f69e95fe716b74e
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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