5-Bromo-2-(trifluoromethyl)pyridine → (1-methyl-1H-pyrazol-4-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone

HRID 512209Notes

Reaction equation

HRID 512209 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([F:11])([F:10])[F:9])=[N:6][CH:7]=1.CON(C)[C:15]([C:17]1[CH:18]=[N:19][N:20]([CH3:22])[CH:21]=1)=[O:16]>C1COCC1.[Ni].Cl>[CH3:22][N:20]1[CH:21]=[C:17]([C:15]([C:2]2[CH:7]=[N:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=2)=[O:16])[CH:18]=[N:19]1

Participants

5

Reactant 2

HCID 27611975-Bromo-2-(trifluoromethyl)pyridineHCID 58477471N-methoxy-N,1-dimethyl-1H-pyrazole-4-carboxamide

Product 1

HCID 86716239(1-methyl-1H-pyrazol-4-yl)(6-(trifluoromethyl)pyridin-3-yl)methanoneYield 34.1%

Reagents, catalysts & solvents 2

HCID 86716240Nickel chlorohydrideCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of 5-bromo-2-(trifluoromethyl)pyridine (3.80 g, 16.82 mmol) in THF (24 ml) was cooled at −18° C. A solution of isopropylmagnesium chloride lithium chloride complex in THF (17.97 ml, 14.02 mmol, 0.78 molar) was added dropwise over a period of 30 minutes. The reaction was then cooled at −78° C. kept there for 1½ hour. The reaction was allowed to reach −3° C. before being cooled to −10° C. A solution of N-methoxy-N,1-dimethyl-1H-pyrazole-4-carboxamide (2.372 g, 14.02 mmol) in THF (8 ml) was added dropwise over a period of 5 minutes. The reaction was allowed to warm to room temperature and stirred over night. Cooled to 0° C. and a 2 Ni HCl solution (150 mL) was added slowly. The crude mixture was extracted with AcOEt (3×150 mL), the combined org. phases were washed with brine, dried over MgSO4 and concentrated in vacuo. The crude product was purified by comlumn chromatography to yield (1-methyl-1H-pyrazol-4-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone 1.22 g (34%) as a light yellow solid.

Workup

  1. waitkept there for 1½ hour
  2. customto reach −3° C.
  3. temperaturebefore being cooled to −10° C
  4. temperatureto warm to room temperature
  5. temperatureCooled to 0° C.
  6. extractionThe crude mixture was extracted with AcOEt (3×150 mL)
  7. washphases were washed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by comlumn chromatography

Sources & evidence

ORD record
ord-80c7879f63504d139c3569c86aff482d
Source dataset
uspto-grants-2015_08
Patent number
US09102591B2

Reaction notes

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