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

HRID 2392230Notes

Reaction equation

HRID 2392230 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[CH:17]=[CH:16][CH:15]=[N:14]1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C.CCCCCC>O1CCOCC1.O>[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 4

HCID 11430Potassium CarbonateHCID 702551H-Pyrazole, 1-methyl-2×HCID 21226206Ethyl acetate hexaneHCID 57826388Methyl 4-bromo-5-chlorothiophene-2-carboxylate

Product 1

HCID 57826577Methyl 5-chloro-4-(1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxylateYield 34%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of methyl 4-bromo-5-chloro-2-thiophenecarboxylate (2.56 g, 10.00 mmol)[prepared according to Example 95], 5-(5,5-dimethyl)-1,3,2-dioxaborinane-2-yl)-1-methyl-1H-pyrazole (3.88 g, 20.0 mmol)[prepared according to Preparation 7], potassium carbonate (4.15 g, 30.0 mmol) and 1,1′-bis(diphenylphosphino)ferrocenedichloro palladium (II) dichloromethane complex (0.073 g, 0.1 mmol) in 1,4-Dioxane (12 mL) and water (3.00 mL) were heated at 80° C. in a sealed tube. After 3 hrs, another batch of 5-(5,5-dimethyl)-1,3,2-dioxaborinane-2-yl)-1-methyl-1H-pyrazole (1.94 g, 10.0 mmol) and 1,1′-bis(diphenylphosphino)ferrocenedichloro palladium (II) dichloromethane complex (0.073 g, 0.1 mmol) were added. After 2 hr, the mixture was concentrated and purified by silica gel eluting with 0-35% ethyl acetate/hexane affording the title compound as a yellow solid (1.74 g, 3.35 mmol, 34%): LC-MS (ES) m/z 257 (M+H)+.

Workup

  1. waitAfter 2 hr
  2. concentrationthe mixture was concentrated

Sources & evidence

ORD record
ord-c5200b90459145baae4c70ae5ccac60a
Source dataset
uspto-grants-2012_09
Patent number
US08273782B2

Reaction notes

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