反应详情

5-Methylimidazo[1,5-a]pyridine [J. Org. Chem. 40, 1210 (1975), 424.7 g]is charged into a 12 liter flask equipped with mechanical stirrer, thermometer and nitrogen atmosphere. Dry tetrahydrofuran (THF, 3,000 ml) is charged into the flask and the resulting solution is cooled to -65° in a dry ice/acetone bath. n-Butyllithium (1.0 mole, 2.4 N in hexane) is poured into the flask all at once under a nitrogen atmosphere. The temperature rises to -32°. The mixture is recooled to -50° and a second mole of n-butyllithium is charged in the same manner. A second temperature rise occurs and after again cooling to -50°, a third mole of the n-butyl-lithium is charged into the reactor. The reaction mixture is then stirred for twenty minutes, the temperature drops to -65°. To this stirring solution a cold (-67°) solution of 5-bromo-1,1,1-triethoxypentane (606.9 g) in 500 ml of THF is added as rapidly as possible, raising the temperature to -25°. The reaction mixture is then warmed to -15° and stirred for 2 hours. Acetic acid (50 ml) is added and most of the solvent is removed under vacuum. The residue is taken up in 2,000 ml of ethyl ether; acetic acid (100 ml), and 12 N HCl (100 ml) are added while the reaction mixture is cooled to 0°. After 15 to 20 minutes, ice-cold 7.5 N ammonium hydroxide (1000 ml) is added. The organic phase is separated and the aqueous is washed again with ethyl ether (500 ml). The pH of the aqueous is adjusted to 9 with ammonium hydroxide and extracted again wth ethyl ether (500 ml). The combined ether extracts are washed with a dilute sodium chloride solution basified to pH 13-14 with potassium hydroxide. The ether extract is treated with charcoal and magnesium sulfate. The mixture is filtered and evaporated to give a dark oil which is dried at 2mm Hg. The oil is distilled under high vaccuum to give 5-(5-ethoxycarbonylpentyl)-imidazo[1,5-a]pyridine of Example 1, boiling at 220°/0.2 mm Hg.

1. customequipped with mechanical stirrer
2. temperaturethe resulting solution is cooled to -65° in a dry ice/acetone bath
3. customrises to -32°
4. customis recooled to -50°
5. temperatureafter again cooling to -50°
6. customdrops to -65°
7. temperatureraising the temperature to -25°
8. temperatureThe reaction mixture is then warmed to -15°
9. stirringstirred for 2 hours
10. customis removed under vacuum
11. additionacetic acid (100 ml), and 12 N HCl (100 ml) are added while the reaction mixture
12. temperatureis cooled to 0°
13. additionice-cold 7.5 N ammonium hydroxide (1000 ml) is added
14. customThe organic phase is separated
15. washthe aqueous is washed again with ethyl ether (500 ml)
16. extractionextracted again wth ethyl ether (500 ml)
17. washThe combined ether extracts are washed with a dilute sodium chloride solution
18. extractionThe ether extract
19. additionis treated with charcoal and magnesium sulfate
20. filtrationThe mixture is filtered
21. customevaporated
22. customto give a dark oil which
23. customis dried at 2mm Hg
24. distillationThe oil is distilled under high vaccuum