反应详情

3-Methyl-5-[3-(2-piperidin-1-yl-ethylamino)-propyl]-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester 32a (225 mg, 0.534 mmol) was dissolved in 5 ml of dry toluene under stirring, the reaction system was cooled in an ice-water bath, and added with a solution of trimethyl aluminum in toluene (0.534 ml, 2 mol/L, 1.07 mmol) under an argon atmosphere. Upon completion of the addition, the reaction system was stirred for 20 minutes at room temperature until no white smoke was released, refluxed for another 3 hours in an oil bath. After thin lay chromatography showed the disappearance of starting materials, the oil bath was removed, the reaction mixture was added with saturated brine (10 ml) and ethyl acetate (20 ml), stirred for 15 minutes at room temperature and filtered. The filter cake was washed with ethyl acetate (10 ml×3). The filtrate was extracted with ethyl acetate (10 ml×2). The combined organic extracts were washed with saturated brine (10 ml×2), dried over anhydrous magnesium sulfate, filtered to remove the drying agent and concentrated under reduced pressure to obtain the title compound 3-methyl-4-oxo-5-(2-piperidin-1-yl-ethyl)-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carboxylic acid tert-butyl ester 32b (105 mg) as a colorless oil to be used directly in the next step.

1. temperaturethe reaction system was cooled in an ice-water bath
2. additionUpon completion of the addition
3. stirringthe reaction system was stirred for 20 minutes at room temperature until no white smoke
4. temperaturerefluxed for another 3 hours in an oil bath
5. customthe oil bath was removed
6. additionthe reaction mixture was added with saturated brine (10 ml) and ethyl acetate (20 ml)
7. stirringstirred for 15 minutes at room temperature
8. filtrationfiltered
9. washThe filter cake was washed with ethyl acetate (10 ml×3)
10. extractionThe filtrate was extracted with ethyl acetate (10 ml×2)
11. washThe combined organic extracts were washed with saturated brine (10 ml×2)
12. dry with materialdried over anhydrous magnesium sulfate
13. filtrationfiltered
14. customto remove the drying agent
15. concentrationconcentrated under reduced pressure