反应 #355782

反应方程式

4,4,4-trifluoro-3-methyl-2-butenoic acid

4-(methylthio)benzonitrile

diisopropylamine

n-butyllithium

→

title product

收率 43.7%

4-(Trifluoromethyl)-6-[4-(methylthio)phenyl]-2-pyridone

收率 43.7%

溶剂

THF

THF

—

hexanes

THF

water

反应条件

后处理

1. 1
   workup.STIRRINGstirred for 30 minutes
2. 2
   温度before being cooled to 0° C.
3. 3
   workup.ADDITIONUpon complete addition
4. 4
   温度the reaction was heated
5. 5
   温度at reflux for 14 hours
6. 6
   温度After cooling
7. 7
   萃取the mixture extracted with ethyl acetate (250 mL)
8. 8
   干燥The organic phase was dried over sodium sulfate
9. 9
   过滤filtered
10. 10
    浓缩concentrated in vacuo
11. 11
    其他the resulting residue purified by silica chromatography
12. 12
    洗涤eluting with 1:1 ethyl acetate/cyclohexane

实验过程

To a stirred solution of diisopropylamine (11.5 mL, 81.8 mmol) in THF (75 mL) at 0° C. was added n-butyllithium (51.1 mL of a 1.6M solution in hexanes, 81.8 mmol). After stirring for 15 minutes, a solution of 4,4,4-trifluoro-3-methyl-2-butenoic acid (6.0 g, 38.9 mmol) in THF (10 mL) was added dropwise. The reaction was allowed to warm to room temperature and stirred for 30 minutes before being cooled to 0° C. and treated dropwise with a solution of 4-(methylthio)benzonitrile (2.91 g, 19.5 mmol) in THF (10 mL). Upon complete addition, the reaction was heated at reflux for 14 hours. After cooling, water (200 mL) was added and the mixture extracted with ethyl acetate (250 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo and the resulting residue purified by silica chromatography eluting with 1:1 ethyl acetate/cyclohexane to give the title product (2.43 g) LC retention time 3.10 mins MS m/z 286 (MH+).

来源