Réaction #544722

Équation de réaction

HCl

tert-butylnitrite

aniline

[4-amino-3-(3-bromo-5-cyano-phenoxy)-2-fluoro-phenyl]-acetic acid ethyl ester

→

[4-chloro-3-(3-bromo-5-cyano-phenoxy)-2-fluoro-phenyl]-acetic acid ethyl ester

Rendement 64.0%

Solvants

CH3CN

Conditions de réaction

Traitement

1. 1
   Autrehad been prepared under nitrogen
2. 2
   TempératureThe reaction temperature was maintained at 60° C. for 2 h
3. 3
   Températurecooled to 0° C
4. 4
   Extractionthe mixture was extracted with 1:1 EtOAc/hexanes (3×75 mL)
5. 5
   LavageThe combined organics were washed with brine (75 mL)
6. 6
   Séchagedried over anhydrous MgSO4
7. 7
   Autreevaporated
8. 8
   AutreThe remaining oil was purified by flash chromatography on silica gel (0% to 30% EtOAc/Hexanes)

Mode opératoire

The aniline 117b (3.98 g, 10.10 mmol) was dissolved in anhydrous CH3CN (35 mL) under nitrogen. This solution was then added dropwise to a mixture of tert-butylnitrite (2.40 mL, 20.20 mmol) and CuCl2 (2.72 g, 20.20 mmol) that had been prepared under nitrogen and warmed to 60° C. The reaction temperature was maintained at 60° C. for 2 h, then cooled to 0° C. A 5% aqueous HCl solution (80 mL) was added, and the mixture was extracted with 1:1 EtOAc/hexanes (3×75 mL). The combined organics were washed with brine (75 mL), dried over anhydrous MgSO4, and evaporated. The remaining oil was purified by flash chromatography on silica gel (0% to 30% EtOAc/Hexanes) to provide 2.67 g (64%) of the [4-chloro-3-(3-bromo-5-cyano-phenoxy)-2-fluoro-phenyl]-acetic acid ethyl ester (117c).

Source