Potassium Carbonate → methyl 1-methyl-5-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrole-3-carboxylate

HRID 1967116Notes

Reaction equation

HRID 1967116 reaction equation
Br[C:2]1[N:6]([CH3:7])[CH:5]=[C:4]([C:8]([O:10][CH3:11])=[O:9])[CH:3]=1.[CH3:12][N:13]1[C:17](B2OC(C)(C)C(C)(C)O2)=[CH:16][CH:15]=[N:14]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:7][N:6]1[C:2]([C:17]2[N:13]([CH3:12])[N:14]=[CH:15][CH:16]=2)=[CH:3][C:4]([C:8]([O:10][CH3:11])=[O:9])=[CH:5]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole2×HCID 58172921methyl 5-bromo-1-methyl-1H-pyrrole-3-carboxylate

Product 1

HCID 58172926methyl 1-methyl-5-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrole-3-carboxylateYield 30.8%

Reagents, catalysts & solvents 3

HCID 178418851HCID 178418851, compoundCatalyst2×HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of methyl 5-bromo-1-methyl-1H-pyrrole-3-carboxylate (950 mg, 4.36 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1088 mg, 5.23 mmol)[prepared according to Preparation 3], potassium carbonate (3011 mg, 21.78 mmol) and bis(tri-t-butylphosphine)palladium(0) (111 mg, 0.218 mmol) in 1,4-Dioxane (18.200 ml) and Water (3.64 ml) was stirred at 80° C. in a sealed tube for 1 h. Additional 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1088 mg, 5.23 mmol) and bis(tri-t-butylphosphine)palladium(0) (111 mg, 0.218 mmol) were added and the solution stirred for 1 h. The reaction mixture was then partitioned between H2O-DCM and the aqueous phase was washed several times with DCM. The combined organic fractions were dried over Na2SO4, concentrated and purified via column chromatography (silica, 4-25% EtOAc in hexanes) yielding methyl 1-methyl-5-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrole-3-carboxylate (300 mg, 1.341 mmol, 30.8% yield) as a clear oil: LCMS m/e ES 220 (M+H)+.

Workup

  1. customThe reaction mixture was then partitioned between H2O-DCM
  2. washthe aqueous phase was washed several times with DCM
  3. dry with materialThe combined organic fractions were dried over Na2SO4
  4. concentrationconcentrated
  5. custompurified via column chromatography (silica, 4-25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-0f0585a844fe41aba9c40997441613cf
Source dataset
uspto-grants-2013_04
Patent number
US08420690B2

Reaction notes

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