反应详情

温度

97.5 °C

Into a 500-ml flask equipped with a reflux condenser, thermometer and stirrer were placed 43.5 g (0.10 mole) of ethyl ester of 1-(2'-cyanobiphenyl-4-yl)methyl-4-(1-hydroxy-1-methylethyl) -2-propylimidazole-5-carboxylic acid, 19.5 g (0.30 mole) of sodium azide, 41.3 g (0.30 mole) of triethylamine hydrochloride and 206 ml of toluene. The mixture was heated with stirring to a temperature of 95 to 100° C. to undergo a reaction for 24 hours. After completion of the reaction, the reaction mixture was cooled to room temperature. Then, 35.0 g (0.42 mole) of a 48 wt % aqueous solution of NaOH and 335 ml of water were added. The mixture was fractionated after 2 hours' stirring at room temperature. The aqueous layer was washed and fractionated with the addition of 103 ml of toluene. The aqueous layer was adjusted to a pH of 2 to 3.5 with 36 wt % hydrochloric acid to separate out crystals, which were collected by filtration and dried. The crystals were heated, washed with methanol with stirring, cooled, filtered for collection and dried, giving 32.6 g (0.07 mole) of 4-(1-hydroxy-1-methylethyl) -2-propyl-1-{4-[2-(tetrazole-5-yl)phenyl]phenyl}methylimidazole-5-carboxylic acid (yield 72.4% based on ethyl ester of 1-(2'-cyanobiphenyl-4-yl)methyl-4-(1-hydroxy-1-methylethyl) -2-propylimidazole-5-carboxylic acid). The reaction is illustrated below with chemical formulas. ##STR29##

1. customInto a 500-ml flask equipped with a reflux condenser
2. customthermometer and stirrer were placed
3. temperatureThe mixture was heated
4. customa reaction for 24 hours
5. customAfter completion of the reaction
6. temperaturethe reaction mixture was cooled to room temperature
7. stirring' stirring at room temperature
8. washThe aqueous layer was washed
9. additionfractionated with the addition of 103 ml of toluene
10. customto separate out crystals, which
11. filtrationwere collected by filtration
12. customdried
13. temperatureThe crystals were heated
14. washwashed with methanol
15. stirringwith stirring
16. temperaturecooled
17. filtrationfiltered for collection
18. customdried