反应详情

温度

70 °C

To a suspension of methyl 3-[4-(7-chloro-2-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepin-11-yl)piperazin-1-yl]-2,2-dimethylpropanoate (28.0 g, 65.27 mmoles) in a mixture of isopropyl alcohol (150 mL) and water (150 mL) add sodium hydroxide (3 equiv; 7.83 g, 195.82 mmoles) and heat at 70° C. for 4 h to give a clear solution. Heat at 70° C. for a further 1 h then cool slightly. Add 5M hydrochloric acid to give pH 8 and precipitate a white solid. Add further 5M hydrochloric acid to give a pH between 6.5 and 7. Reduce the volume of solvent by half and then chill the flask in a fridge for 0.5 h. Collect the resulting white solid by filtration and dry overnight in a vacuum oven at 40° C. over phosphorus pentoxide to give 3-[4-(7-chloro-2-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepin-11-yl)piperazin-1-yl]-2,2-dimethylpropanoic acid (26.5 g, 98% yield). MS (m/z): 415.3 (M+1). DSC melting point=246.5° C. (onset).

1. customto give a clear solution
2. temperatureHeat at 70° C. for a further 1 h
3. temperaturethen cool slightly
4. customto give pH 8
5. customprecipitate a white solid
6. additionAdd further 5M hydrochloric acid
7. customto give a pH between 6.5 and 7
8. temperaturechill the flask in a fridge for 0.5 h
9. customCollect the resulting white solid
10. filtrationby filtration
11. dry with materialdry overnight in a vacuum oven at 40° C. over phosphorus pentoxide