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

HRID 2392049Notes

Reaction equation

HRID 2392049 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:18](=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]>[CH3:17][N:5]1[C:6]([C:7]2[CH:8]=[C:9]([C:13]([O:15][CH3:16])=[O:14])[S:10][C:11]=2[CH3:12])=[C:2]([CH3:18])[CH:3]=[N:4]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 57826393methyl 4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-methyl-2-thiophenecarboxylate

Product 1

HCID 57826452methyl 4-(1,4-dimethyl-1H-pyrazol-5-yl)-5-methyl-2-thiophenecarboxylateYield 72.1%

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-methyl-2-thiophenecarboxylate (420 mg, 1.33 mmol), potassium carbonate (921 mg, 6.66 mmol), PdCl2(dppf) (98 mg, 0.13 mmol) and trimethylboroxine (0.371 ml, 2.67 mmol) in N,N-dimethylformamide (6.663 ml) was stirred at 110° C. in a sealed tube for 2 h. This reaction was run in two batches (100 mg and 420 mg) which were combined and partitioned between H2O-DCM. The aqueous phase was washed several times with DCM and 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-methyl-2-thiophenecarboxylate (240 mg, 58%) as a yellow oil: LCMS (ES) m/e 251 (M+H)+.

Workup

  1. custompartitioned 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-475b0969a9ce4c1eab764ed4a389d857
Source dataset
uspto-grants-2012_09
Patent number
US08273782B2

Reaction notes

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