反应详情

A solution of 2-ethyl-4-[(2'-(2-tributylstannyl-2H-tetrazol-5-yl)biphenyl-4-yl)methoxy]quinoline in toluene (15 ml), prepared in situ by refluxing for 90 hours a mixture of 4'-[(2-ethylquinolin-4-yloxy)methyl]biphenyl-2-carbonitrile (0.9 g) and a solution of tributyltin azide in toluene (15 ml) [the latter prepared by reaction of tributyltin chloride (3.3 g) and sodium azide (1.13 g) in water (22.5 ml) at ambient temperature for 4 hours, followed by extraction with toluene and azeotropic removal of water from the extract to leave a volume of 15 ml], was added slowly over 1 hour to a solution of sodium nitrite (2.5 g) in water (10 ml) containing 12% w/v hydrochloric acid (10 ml), maintaining the temperature of the mixture below 5° C. A solution of sulphamic acid (1.43 g) in water (10 ml) was then added, maintaining the temperature below 5° C., and the mixture stirred for 1 hour. The resultant suspended semi-solid was collected by filtration and washed with water (3×10 ml), followed by toluene (10 ml). The semi-solid was then added to tetrahydrofuran (THF) (40 ml), which caused the product to dissolve and then crystallise as a white solid. After cooling for one hour the solid was collected by filtration, washed with THF (5 ml) and dried to give 2-ethyl-4-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methoxy]-quinoline hydrochloride; NMR similar to the product obtained from Example 10.

1. temperatureby refluxing for 90 hours
2. extractionfollowed by extraction with toluene and azeotropic removal of water from the
3. extractionextract
4. customto leave a volume of 15 ml],
5. additioncontaining 12%
6. temperaturemaintaining the temperature of the mixture below 5° C
7. temperaturemaintaining the temperature below 5° C.
8. filtrationwas collected by filtration
9. washwashed with water (3×10 ml)
10. additionThe semi-solid was then added to tetrahydrofuran (THF) (40 ml), which
11. dissolutionto dissolve
12. customcrystallise as a white solid
13. temperatureAfter cooling for one hour the solid
14. filtrationwas collected by filtration
15. washwashed with THF (5 ml)
16. customdried