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

HRID 512209Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 512209
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

Komponenten

5

Edukt 2

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

Produkt 1

HCID 86716239(1-methyl-1H-pyrazol-4-yl)(6-(trifluoromethyl)pyridin-3-yl)methanoneAusbeute 34,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 86716240Nickel chlorohydrideKatalysatorHCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-80c7879f63504d139c3569c86aff482d
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09102591B2

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