Reacción #8319

Ecuación de reacción

citric acid

6-trifluoromethyl-pyridine-2-carbothioic acid S-(4-chloro-phenyl) ester

4-fluorophenylacetonitrile

potassium bis(trimethylsilyl)amide

→

2-(4-fluoro-phenyl)-3-oxo-3-(6-trifluoromethyl-pyridin-2-yl)-propionitrile

Rendimiento 66.0%

Disolventes

methylene chloride

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroto warn to room temperature
2. 2
   Temperaturathen warmed
3. 3
   Temperaturato reflux for 10 min, at which time the reaction
4. 4
   Temperaturato cool
5. 5
   Extracciónextracted into methylene chloride
6. 6
   SecadoThe methylene chloride solution is dried over magnesium sulfate
7. 7
   Concentraciónconcentrated in vacuo
8. 8
   OtroThe residue is purified on a silica gel cartridge
9. 9
   Otroprepared with hexane
10. 10
    Lavadothen eluted with methylene chloride

Procedimiento

A solution of 4-fluorophenylacetonitrile (0.12 mL, 1.0 mmol) in dry tetrahydrofuran (2 mL) is treated dropwise with potassium bis(trimethylsilyl)amide (0.5 M toluene, 3.0 mL, 1.5 mmol) at 0° C. under an atmosphere of nitrogen. The mixture is stirred 10 min then 6-trifluoromethyl-pyridine-2-carbothioic acid S-(4-chloro-phenyl) ester is added all at once. The mixture is allowed to warn to room temperature then warmed to reflux for 10 min, at which time the reaction is complete by TLC (methylene chloride). The mixture is allowed to cool then poured into 10% citric acid and extracted into methylene chloride. The methylene chloride solution is dried over magnesium sulfate and concentrated in vacuo. The residue is purified on a silica gel cartridge prepared with hexane then eluted with methylene chloride to yield 204 mg (66%) 2-(4-fluoro-phenyl)-3-oxo-3-(6-trifluoromethyl-pyridin-2-yl)-propionitrile. MS ES− m/z 307 (M−1).

Fuente