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

HRID 2392081Notes

Reaction equation

HRID 2392081 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]([CH3:18])[C:6]=1[C:7]1[CH:8]=[C:9]([C:14]([O:16][CH3:17])=[O:15])[S:10][C:11]=1[CH2:12][CH3:13].[C:19](=O)([O-])[O-].[K+].[K+].CB1OB(C)OB(C)O1>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:18][N:5]1[C:6]([C:7]2[CH:8]=[C:9]([C:14]([O:16][CH3:17])=[O:15])[S:10][C:11]=2[CH2:12][CH3:13])=[C:2]([CH3:19])[CH:3]=[N:4]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 57826735methyl 4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-ethyl-2-thiophenecarboxylate

Product 1

HCID 57826857methyl 4-(1,4-dimethyl-1H-pyrazol-5-yl)-5-ethyl-2-thiophenecarboxylateYield 56%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of methyl 4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-ethyl-2-thiophenecarboxylate (300 mg, 0.911 mmol), potassium carbonate (630 mg, 4.56 mmol), PdCl2(dppf) (66.7 mg, 0.091 mmol) and trimethylboroxin (0.25 ml, 1.82 mmol) in N,N-dimethylformamide (9.1 ml) was stirred at 110° 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 (10-50% EtOAc in hexanes) affording methyl 4-(1,4-dimethyl-1H-pyrazol-5-yl)-5-ethyl-2-thiophenecarboxylate (143 mg, 0.51 mmol, 56% yield) as a yellow oil: LCMS (ES) m/z=265 (M+H)+.

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 (10-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-bfc21b4293c1483fa5953a782f8d9fe7
Source dataset
uspto-grants-2012_09
Patent number
US08273782B2

Reaction notes

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