Potassium Carbonate → 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid [2-(3-chloro-5-trifluoromethyl-pyridin-2-yloxy)-1-methyl-ethyl]-amide

HRID 2189958Notes

Reaction equation

HRID 2189958 reaction equation
[OH:1][CH2:2][CH:3]([NH:5][C:6]([C:8]1[C:9]([CH:14]([F:16])[F:15])=[N:10][N:11]([CH3:13])[CH:12]=1)=[O:7])[CH3:4].Br[C:18]1[C:23]([Cl:24])=[CH:22][C:21]([C:25]([F:28])([F:27])[F:26])=[CH:20][N:19]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Cl:24][C:23]1[C:18]([O:1][CH2:2][CH:3]([NH:5][C:6]([C:8]2[C:9]([CH:14]([F:16])[F:15])=[N:10][N:11]([CH3:13])[CH:12]=2)=[O:7])[CH3:4])=[N:19][CH:20]=[C:21]([C:25]([F:27])([F:26])[F:28])[CH:22]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27362372-Bromo-3-chloro-5-(trifluoromethyl)pyridineHCID 582314523-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (2-hydroxy-1-methyl-ethyl)-amide

Product 1

HCID 595801713-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid [2-(3-chloro-5-trifluoromethyl-pyridin-2-yloxy)-1-methyl-ethyl]-amideYield 34%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 2.3 g 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (2-hydroxy-1-methyl-ethyl)-amide (10.0 mmol, prepared as described in example P5a) and 2.6 g 2-bromo-3-chloro-5-trifluoromethyl-pyridine (10 mmol) in dimethylformamide (30 ml) is treated at ambient temperature with 2.8 g potassium carbonate (20 mmol). The resulting suspension is stirred at 100° C. for 3 hours, cooled to ambient temperature, poured onto water (200 ml) and extracted with ethyl acetate (2×100 ml). The combined ethyl acetate layers are washed with water (20 ml) and dried over Na2SO4. After removal of the solvent the residue (4.2 g in the form of an oil) is purified by flash chromatography over silica gel (eluent: cyclohexane/ethyl acetate 3:7). 1.4 g (34% of theory) of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid [2-(3-chloro-5-trifluoromethyl-pyridin-2-yloxy)-1-methyl-ethyl]-amide (compound 1.239) is obtained in form of a solid (mp. 115-118° C.).

Workup

  1. temperaturecooled to ambient temperature
  2. additionpoured onto water (200 ml)
  3. extractionextracted with ethyl acetate (2×100 ml)
  4. washThe combined ethyl acetate layers are washed with water (20 ml)
  5. dry with materialdried over Na2SO4
  6. customAfter removal of the solvent the residue (4.2 g in the form of an oil)
  7. customis purified by flash chromatography over silica gel (eluent: cyclohexane/ethyl acetate 3:7)

Sources & evidence

ORD record
ord-6d5f0a43c9c84c798de0a63b411bbb14
Source dataset
uspto-grants-2012_12
Patent number
US08324263B2

Reaction notes

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