Réaction #76643

Équation de réaction

(phenylmethoxy)-N-vinylcarboxamide

4-bromo-2-fluorobenzonitrile

→

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

Rendement 86.0%

Solvants

THF

THF

THF

Conditions de réaction

Traitement

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

Mode opératoire

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).

Source