反应 #62216

反应方程式

4-Methoxyaniline

pyridine-4-carboxaldehyde

potassium carbonate

tosylmethylisocyanide

→

title compound

收率 56.0%

4-(1-(4-methoxyphenyl)-1H-imidazol-5-yl)pyridine

收率 56.0%

溶剂

methanol

1,2-dimethoxyethane

toluene

反应条件

后处理

1. 1
   温度reflux condensor
2. 2
   温度was heated
3. 3
   温度at reflux
4. 4
   其他The toluene was removed via distillation through the Dean-Stark sidearm
5. 5
   workup.DISSOLUTIONthe residue was dissolved in methanol (100 mL)
6. 6
   温度was heated
7. 7
   温度at reflux for 3 hours
8. 8
   其他the solvent was removed in vacuo
9. 9
   workup.DISSOLUTIONthe residue was dissolved in methylene chloride
10. 10
    洗涤was washed with brine
11. 11
    萃取The brine layer was extracted with methylene chloride
12. 12
    干燥the combined organic layers were dried (MgSO4)
13. 13
    过滤were filtered
14. 14
    浓缩were concentrated in vacuo
15. 15
    其他The residue was purified by silica gel chromatography with ethyl acetate—hexanes—methanol (80:20:0 to 76:19:5)

实验过程

4-Methoxyaniline (2.46 g, 20 mmol) and pyridine-4-carboxaldehyde (1.9 mL, 10 mmol) in toluene (110 mL) in a flask attached to a Dean-Stark trap and reflux condensor was heated at reflux. After 40 hours, the reaction was complete by infrared spectral analysis and mass spectral analysis. The toluene was removed via distillation through the Dean-Stark sidearm, the residue was dissolved in methanol (100 mL) and ca. ½ of the crude imine (ca. 10 mmol, 50 mL of methanol solution) was diluted with methanol (20 mL) and 1,2-dimethoxyethane (20 mL). The solution was then treated with potassium carbonate (2.76 g, 20 mmol) and tosylmethylisocyanide (TOSMIC, 2.93 g, 15 mmol) and was heated at reflux for 3 hours. After cooling to room temperature, the solvent was removed in vacuo, and the residue was dissolved in methylene chloride and was washed with brine. The brine layer was extracted with methylene chloride and the combined organic layers were dried (MgSO4), were filtered, and were concentrated in vacuo. The residue was purified by silica gel chromatography with ethyl acetate—hexanes—methanol (80:20:0 to 76:19:5) to afford 1.4 g (56% yield) of the title compound; diagnostic 13C NMR signals (100 MHz, CDCl3) δ 160.039, 150.161, 141.009, 137.240, 130.839, 129.179, 127.287, 121.597, 115.106, 55.801; MS (AP/Cl) 252.4 (M+H)+.

来源