Reaktion #666046

Reaktionsgleichung

N-[[1-(5-bromo-3-chloro-2-pyridyl)cyclopropyl]methyl]-2-(trifluoromethyl)benzamide

N—[[1-(5-bromo-3-chloro-2-pyridyl)cyclopropyl]methyl]-2-(trifluoromethyl)benzamide

potassium cyclopropyltrifluoroborate

cesium carbonate

→

N-[[1-(3-chloro-5-cyclopropyl-2-pyridyl)cyclopropyl]methyl]-2-(trifluoromethyl)benzamide

Ausbeute 44.7%

Lösungsmittel

—

mixture

toluene

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction mixture was degassed with argon for 1 min
2. 2
   workup.ADDITION14 mg of [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) was added
3. 3
   SonstigeThe vial was sealed
4. 4
   workup.WAITat 130° C. for 30 min
5. 5
   TemperaturThen the mixture was cooled to ambient temperature
6. 6
   workup.ADDITIONwater was added
7. 7
   Extraktionthe reaction mixture was extracted with dichloromethane
8. 8
   TrocknenThe organic phase was dried with anhydrous sodium sulfate
9. 9
   Filtrationfiltered
10. 10
    Einengenconcentrated
11. 11
    SonstigeCrude material was obtained as a brown sticky solid, which
12. 12
    Sonstigewas purified by flash chromatography on silica gel with heptane/ethyl acetate as a solvent

Vorschrift

150 mg of N-[[1-(5-bromo-3-chloro-2-pyridyl)cyclopropyl]methyl]-2-(trifluoromethyl)benzamide (step 4), 61 mg potassium cyclopropyltrifluoroborate and 340 mg cesium carbonate were dissolved in 3 ml of a mixture of toluene and water (3:1) in a microwave vial. The reaction mixture was degassed with argon for 1 min and 14 mg of [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) was added. The vial was sealed and the reaction mixture was then stirred at 100° C. in a microwave reactor for 30 min, then at 130° C. for 30 min. Then the mixture was cooled to ambient temperature, water was added and the reaction mixture was extracted with dichloromethane. The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. Crude material was obtained as a brown sticky solid, which was purified by flash chromatography on silica gel with heptane/ethyl acetate as a solvent. Thus, 61 mg of N-[[1-(3-chloro-5-cyclopropyl-2-pyridyl)cyclopropyl]methyl]-2-(trifluoromethyl)benzamide was obtained as a pale yellow sticky solid. 1H-NMR (CDCl3): 8.19 ppm (d, 1H), 7.65 ppm (d, 1H), 7.52 ppm (m, 2H), 7.40 ppm (d, 1H), 7.30 ppm (d, 1H), 6.20 ppm (s, 1H, broad), 3.68 ppm (d, 2H), 1.85 ppm (m, 1H), 1.05 ppm (m, 5H), 0.88 ppm (m, 1H), 0.70 ppm (m, 2H).

Quelle