Potassium Carbonate → methyl 5-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate

HRID 2392227Notes

Reaction equation

HRID 2392227 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]([O:10][CH3:11])=[O:9])[S:5][C:6]=1[CH3:7].C(=O)([O-])[O-].[K+].[K+].[CH3:18][N:19]1[C:23](B2OC(C)(C)C(C)(C)O2)=[CH:22][CH:21]=[N:20]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>[CH3:7][C:6]1[S:5][C:4]([C:8]([O:10][CH3:11])=[O:9])=[CH:3][C:2]=1[C:23]1[N:19]([CH3:18])[N:20]=[CH:21][CH:22]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 18536848Methyl 4-bromo-5-methylthiophene-2-carboxylate

Product 1

HCID 57826485methyl 5-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate

Reagents, catalysts & solvents 3

HCID 178418851HCID 178418851, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of methyl 4-bromo-5-methyl-2-thiophenecarboxylate (2 g, 8.51 mmol)[prepared in Preparation 10], potassium carbonate (5.88 g, 42.5 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.12 g, 10.21 mmol)[prepared according to Preparation 7] and bis(tri-t-butylphosphine)palladium(0) (0.22 g, 0.43 mmol) in 1,4-Dioxane (35 ml) and H2O (7 ml) was stirred at 80° C. in a sealed tube 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, 25% EtOAc in hexanes) affording methyl 5-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate. This reaction was run in several batches (1 g, 3×2 g) which were combined for workup and purification affording the title compound (5.5 g, 78% combined yield) as a viscous yellow oil: LC-MS (ES) m/e 236 (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, 25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-38e5be7cf14c4be58710bc8be3f57c30
Source dataset
uspto-grants-2012_09
Patent number
US08273782B2

Reaction notes

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