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

HRID 1961175Notes

Reaction equation

HRID 1961175 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[O:5][C:6]=1[CH2:7][CH3:8].C(=O)([O-])[O-].[K+].[K+].[CH3:19][N:20]1[C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][CH:22]=[N:21]1>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>[CH2:7]([C:6]1[O:5][C:4]([C:9]([O:11][CH3:12])=[O:10])=[CH:3][C:2]=1[C:24]1[N:20]([CH3:19])[N:21]=[CH:22][CH:23]=1)[CH3:8]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole2×HCID 57826652Methyl 4-bromo-5-ethyl-2-furancarboxylate

Product 1

HCID 57826562methyl 5-ethyl-4-(1-methyl-1H-pyrazol-5-yl)-2-furancarboxylateYield 71.4%

Reagents, catalysts & solvents 1

HCID 178418851HCID 178418851, compoundCatalyst2×

Conditions

Temperature
80 °C

Procedure

A solution of methyl 4-bromo-5-ethyl-2-furancarboxylate (1.1 g, 4.72 mmol), potassium carbonate (3.26 g, 23.60 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.178 g, 5.66 mmol)[prepared according to Preparation 7] and bis(tri-t-butylphosphine)palladium(0) (0.121 g, 0.24 mmol) were combined in a sealed tube and stirred at 80° C. for 1 h. LCMS showed 4:1 pdt/sm. Additional 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.178 g, 5.66 mmol) and bis(tri-t-butylphosphine)palladium(0) (0.121 g, 0.24 mmol) were added and the solution stirred an additional 2 h where crude LCMS showed nearly complete conversion to product. The reaction contents were 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 (10-50% EtOAc in hexanes) affording methyl 5-ethyl-4-(1-methyl-1H-pyrazol-5-yl)-2-furancarboxylate (950 mg, 3.37 mmol, 71.3% yield) as a yellow oil: LCMS (ES) m/e 235 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-b0a27d3bf0cc45058ea07b3e6fc506d5
Source dataset
uspto-grants-2013_04
Patent number
US08410158B2

Reaction notes

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