Reaktion #62216

Reaktionsgleichung

4-Methoxyaniline

pyridine-4-carboxaldehyde

potassium carbonate

tosylmethylisocyanide

→

title compound

Ausbeute 56.0%

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

Ausbeute 56.0%

Lösungsmittel

methanol

1,2-dimethoxyethane

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturreflux condensor
2. 2
   Temperaturwas heated
3. 3
   Temperaturat reflux
4. 4
   SonstigeThe toluene was removed via distillation through the Dean-Stark sidearm
5. 5
   workup.DISSOLUTIONthe residue was dissolved in methanol (100 mL)
6. 6
   Temperaturwas heated
7. 7
   Temperaturat reflux for 3 hours
8. 8
   Sonstigethe solvent was removed in vacuo
9. 9
   workup.DISSOLUTIONthe residue was dissolved in methylene chloride
10. 10
    Waschenwas washed with brine
11. 11
    ExtraktionThe brine layer was extracted with methylene chloride
12. 12
    Trocknenthe combined organic layers were dried (MgSO4)
13. 13
    Filtrationwere filtered
14. 14
    Einengenwere concentrated in vacuo
15. 15
    SonstigeThe residue was purified by silica gel chromatography with ethyl acetate—hexanes—methanol (80:20:0 to 76:19:5)

Vorschrift

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)+.

Quelle