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

HRID 2047356Notes

Reaction equation

HRID 2047356 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]([O:10][CH3:11])=[O:9])[S:5][C:6]=1[Cl:7].[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>[Cl:7][C:6]1[S:5][C:4]([C:8]([O:10][CH3:11])=[O:9])=[CH:3][C:2]=1[C:17]1[N:13]([CH3:12])[N:14]=[CH:15][CH:16]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 57826388Methyl 4-bromo-5-chlorothiophene-2-carboxylate

Product 1

HCID 57826577Methyl 5-chloro-4-(1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxylateYield 63.7%

Reagents, catalysts & solvents 3

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

Procedure

A solution of methyl 4-bromo-5-chloro-2-thiophenecarboxylate (5 g, 19.57 mmol)[prepared in Preparation 2], 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (4.28 g, 20.55 mmol)[prepared in Preparation 1], potassium carbonate (10.82 g, 78 mmol) and bis(tri-t-butylphosphine)palladium(0) (0.500 g, 0.978 mmol) in 1,4-dioxane (82 ml) and water (16.31 ml) was stirred at 80° C. in a sealed tube for 2 h. The reaction mixture was 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) yielding methyl 5-chloro-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate (3.2 g, 12.47 mmol, 63.7% yield) as a white solid: LCMS m/e ES 257, 259 (M, M+2)+.

Workup

  1. customThe reaction 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 (silica, 25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-3311601579004585a50dd7129c5d30d6
Source dataset
uspto-grants-2013_11
Patent number
US08592475B2

Reaction notes

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