反应详情

In a 1 L copper flask was placed 7-benzyl-5,6,7,8-tetrahydro-[2,7]-naphthyridine-4-carbonitrile (44.8 g, 0.18 mol) in ethanol (200 mL). A solution of sodium hydroxide (36 g, 0.9 mol) in water (200 mL) was added and the resulting mixture was refluxed for 8 hr. The reaction mixture was concentrated under reduced pressure. To the residue was added ethanol (150 mL) and toluene (150 mL) and concentrated under reduced pressure. This process was repeated three times. Finally methanol (150 mL) and toluene (150 mL) were added and concentrated under reduced pressure. The solid residue was further dried under high vacuum line overnight. To the residue was added a solution of 30% sulfuric acid in methanol (w/w, 800 mL) and refluxed for 24 hr. The reaction mixture was cooled to room temperature and filtered to remove white solid (inorganic salt). The solid on filter paper was washed with methanol (100 mL) and the filtrate was concentrated under reduced pressure. To the residue was added ice (300 g) and basified with ammonium hydroxide (175 mL. 28-38% ammonia). The mixture was extracted with dichloromethane (2×250 mL). The combined organic layers were washed with brine (150 mL), filtered through 1 PS filter paper and concentrated to give a brown oil. The oil was purified by flash chromatography on silica gel (500 g) with anhydrous sodium sulfate (50 g) on top packed with hexane. The column was eluted with 200 mL portions of 25% ethyl acetate in hexane followed by 50% ethyl acetate in hexane. The eluent containing product was concentrated to give the title compound (39.1 g, 77%) as an oil which solidified on standing. 1H NMR 60 MHz, (CDCl3), δ 8.8 (s, 1H), 8.2 (s, 1H), 7.3 (s, 5H), 3.8 (s, 3H), 3.6 (s, 2H), 3.5 (s, 2H), 3.2 (m, 2H), 2.6 (m, 2H).

1. customIn a 1 L copper flask was placed
2. temperaturethe resulting mixture was refluxed for 8 hr
3. concentrationThe reaction mixture was concentrated under reduced pressure
4. additionTo the residue was added ethanol (150 mL) and toluene (150 mL)
5. concentrationconcentrated under reduced pressure
6. additionFinally methanol (150 mL) and toluene (150 mL) were added
7. concentrationconcentrated under reduced pressure
8. customThe solid residue was further dried under high vacuum line overnight
9. additionTo the residue was added a solution of 30% sulfuric acid in methanol (w/w, 800 mL)
10. temperaturerefluxed for 24 hr
11. filtrationfiltered
12. customto remove white solid (inorganic salt)
13. filtrationThe solid on filter paper
14. washwas washed with methanol (100 mL)
15. concentrationthe filtrate was concentrated under reduced pressure
16. additionTo the residue was added ice (300 g)
17. extractionThe mixture was extracted with dichloromethane (2×250 mL)
18. washThe combined organic layers were washed with brine (150 mL)
19. filtrationfiltered through 1 PS
20. filtrationfilter paper
21. concentrationconcentrated
22. customto give a brown oil
23. customThe oil was purified by flash chromatography on silica gel (500 g) with anhydrous sodium sulfate (50 g) on top
24. washThe column was eluted with 200 mL portions of 25% ethyl acetate in hexane
25. additionThe eluent containing product
26. concentrationwas concentrated