Reaktion #76643

Reaktionsgleichung

(phenylmethoxy)-N-vinylcarboxamide

4-bromo-2-fluorobenzonitrile

→

N-[2-(4-cyano-3-fluorophenyl)ethyl](phenylmethoxy)carboxamide

Ausbeute 86.0%

Lösungsmittel

THF

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeInto a 100 mL single neck flask was placed
2. 2
   TemperaturThe reaction mixture was warmed up to RT
3. 3
   SonstigeThe reaction mixture was quenched with 3N NaOH (2mL)
4. 4
   workup.STIRRINGThe mixture was stirred at RT for 12 hour
5. 5
   Sonstigewas quenched with a 2:1 mixture of pH=7 buffer hydrogen peroxide (10 mL)
6. 6
   ExtraktionThe product was extracted with EtOAc
7. 7
   Sonstigethe organic layer was separated
8. 8
   Waschenwashed twice with H2O
9. 9
   Trocknendried over anhydrous Na2SO4
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated under reduced vacuum
12. 12
    SonstigeThe resulting semi-solid was further purified via flash chromatography (Silica gel, isocratic)
13. 13
    Wascheneluting with a solvent of Hexanes/EtOAc 50%

Vorschrift

Into a 100 mL single neck flask was placed (phenylmethoxy)-N-vinylcarboxamide (5.54 g, 31.25 mmol) in THF (15 mL). The mixture was cooled down to −10° C. while treated dropwise with a solution of 9-BBN dimer (3.81 g, 15.62 mmol) in THF (20 mL). The reaction mixture was warmed up to RT while stirring for additional 2 hours. The reaction mixture was quenched with 3N NaOH (2mL) and the mixture was stirred for 10 minutes before its addition to a solution of 4-bromo-2-fluorobenzonitrile (5 g, 25 mmol) and [1,1′bis(diphenylphosphino)-ferrocene] dichloropalladium (II), PdCl2(dppf), (0.4 g, 0.5 mmol) in THF (10 mL). The mixture was stirred at RT for 12 hour and then was quenched with a 2:1 mixture of pH=7 buffer hydrogen peroxide (10 mL). The product was extracted with EtOAc and the organic layer was separated and washed twice with H2O, dried over anhydrous Na2SO4, filtered, and concentrated under reduced vacuum. The resulting semi-solid was further purified via flash chromatography (Silica gel, isocratic) and eluting with a solvent of Hexanes/EtOAc 50% to provide the intermediate title compound, N-[2-(4-cyano-3-fluorophenyl)ethyl](phenylmethoxy)carboxamide, (6.4 g, 86%) as a white solid. Electron spray M.S. 299 (M*+H).

Quelle