Potassium Carbonate → Methyl 4-(1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxylate

HRID 1961155Notes

Reaction equation

HRID 1961155 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:7]([O:9][CH3:10])=[O:8])[S:5][CH:6]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:17][N:18]1[C:22](B2OC(C)(C)C(C)(C)O2)=[CH:21][CH:20]=[N:19]1>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>[CH3:17][N:18]1[C:22]([C:2]2[CH:3]=[C:4]([C:7]([O:9][CH3:10])=[O:8])[S:5][CH:6]=2)=[CH:21][CH:20]=[N:19]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole2×HCID 12752071Methyl 4-bromothiophene-2-carboxylate

Product 1

HCID 57826540Methyl 4-(1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxylateYield 99.5%

Reagents, catalysts & solvents 3

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

Procedure

A solution of methyl 4-bromo-2-thiophenecarboxylate (2.5 g, 11.31 mmol), potassium carbonate (7.81 g, 56.5 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.59 g, 12.44 mmol)[prepared according to Preparation 7] and bis(tri-t-butylphosphine)palladium(0) (0.289 g, 0.56 mmol) in 1,4-dioxane (47 ml) and water (9 ml) was stirred at 80° C. in a sealed tube for 1 h. 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.59 g, 12.44 mmol) and bis(tri-t-butylphosphine)palladium(0) (0.289 g, 0.56 mmol) were added and the reaction stirred an additional 1 h. The mixture was partitioned between H2O-DCM. The aqueous phase was washed several times with DCM and the combined organic fractions were dried over Na2SO4, concentrated and purified via column chromatography (10-40% EtOAc in hexanes) affording methyl 4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate (2.5 g, 11.25 mmol, 99% yield) as a yellow solid: LCMS (ES) m/e 223 (M+H)+.

Workup

  1. customThe mixture was 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 (10-40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2002c252c8b943db951337ac4cdf12bf
Source dataset
uspto-grants-2013_04
Patent number
US08410158B2

Reaction notes

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