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

HRID 1845489Notes

Reaction equation

HRID 1845489 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]([CH3:17])[C:6]=1[C:7]1[CH:8]=[C:9]([C:13]([O:15][CH3:16])=[O:14])[S:10][C:11]=1[CH3:12].C(=O)([O-])[O-].[K+].[K+].[CH3:24][C:25]1(C)[C:29](C)(C)OB(C(C)=C)O1>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>[CH3:12][C:11]1[S:10][C:9]([C:13]([O:15][CH3:16])=[O:14])=[CH:8][C:7]=1[C:6]1[N:5]([CH3:17])[N:4]=[CH:3][C:2]=1[C:25]([CH3:29])=[CH2:24]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 109974264,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolaneHCID 57826393methyl 4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-methyl-2-thiophenecarboxylate

Product 1

HCID 57826589methyl 5-methyl-4-[1-methyl-4-(1-methylethenyl)-1H-pyrazol-5-yl]-2-thiophenecarboxylateYield 61.1%

Reagents, catalysts & solvents 3

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

Procedure

A solution of methyl 4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-methyl-2-thiophenecarboxylate (300 mg, 0.95 mmol), potassium carbonate (658 mg, 4.76 mmol), bis(tri-t-butylphosphine)palladium(0) (24.32 mg, 0.05 mmol) and 4,4,5,5-tetramethyl-2-(1-methylethenyl)-1,3,2-dioxaborolane (0.18 ml, 0.95 mmol) in 1,4-dioxane (5.3 ml) and H2O (1.0 ml) was stirred at 80° C. in a sealed tube for 12 h. The reaction contents were 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 (10-50% EtOAc in hexanes) affording methyl 5-methyl-4-[1-methyl-4-(1-methylethenyl)-1H-pyrazol-5-yl]-2-thiophenecarboxylate (171 mg, 0.58 mmol, 61% yield) as a yellow oil: LCMS (ES) m/z=276 (M+H)+.

Workup

  1. customThe reaction contents
  2. customwere partitioned between H2O-DCM
  3. washthe aqueous phase was washed several times with DCM
  4. dry with materialThe combined organic fractions were dried over Na2SO4
  5. concentrationconcentrated
  6. custompurified via column chromatography (10-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-7f9c878916cf4badafb7be6ea73993de
Source dataset
uspto-grants-2015_02
Patent number
US08946278B2

Reaction notes

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