تفاعل #8319

معادلة التفاعل

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

المردود 66.0%

المذيبات

methylene chloride

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   أخرىto warn to room temperature
2. 2
   درجة الحرارةthen warmed
3. 3
   درجة الحرارةto reflux for 10 min, at which time the reaction
4. 4
   درجة الحرارةto cool
5. 5
   استخلاصextracted into methylene chloride
6. 6
   تجفيفThe methylene chloride solution is dried over magnesium sulfate
7. 7
   تركيزconcentrated in vacuo
8. 8
   أخرىThe residue is purified on a silica gel cartridge
9. 9
   أخرىprepared with hexane
10. 10
    غسيلthen eluted with methylene chloride

الإجراء التجريبي

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).

المصدر