反应详情

Sodium hydride (60% dispersion in mineral oil, 0.24 g) was added to a stirred solution of 2-propoxybenzimidazole (0.71 g) in DMF (10 ml) under ice-cooling. The mixture was stirred for 20 minutes, to which was added N-triphenylmethyl-5-(4'-bromomethylbiphenyl-2-yl)tetrazole (2.3 g), followed by stirring at room temperature for 5 hours. To the reaction mixture was added ice-water, the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried and concentrated to dryness. The concentrate was dissolved in methanol (50 ml), to which was added 1N-HCl (15 ml), followed by stirring at 60° C. for 2 hours. The reaction mixture was concentrated, to which were added water (15 ml) and ethyl acetate (15 ml). The mixture was made alkaline with 1N NaOH and shaken. The aqueous layer was adjusted to pH 3-4 with 1N-HCl and then extracted with chloroform. The organic layer was washed with water, dried and concentrated to dryness. The concentrate was purified by column chromatography on silica gel to yield crystals. Recrystallization from ethyl acetate-methanol gave colorless crystals (0.58 g, 35%), m.p. 177°-179° C. (decomp.).

1. temperaturecooling
2. stirringby stirring at room temperature for 5 hours
3. extractionthe mixture was extracted with ethyl acetate
4. washThe organic layer was washed with water
5. customdried
6. concentrationconcentrated to dryness
7. dissolutionThe concentrate was dissolved in methanol (50 ml), to which
8. additionwas added 1N-HCl (15 ml)
9. stirringby stirring at 60° C. for 2 hours
10. concentrationThe reaction mixture was concentrated, to which
11. additionwere added water (15 ml) and ethyl acetate (15 ml)
12. stirringshaken
13. extractionextracted with chloroform
14. washThe organic layer was washed with water
15. customdried
16. concentrationconcentrated to dryness
17. customThe concentrate was purified by column chromatography on silica gel
18. customto yield crystals
19. customRecrystallization from ethyl acetate-methanol