反应详情

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 (953 mg, 2.54 mmol) was dissolved in 3 ml of ethanol under stirring, and added dropwise with hydrochloric acid (3.2 ml, 12 mol/L) in an ice-water bath under an argon atmosphere. Upon completion of the addition, the ice-water bath was removed, and the reaction mixture was stirred at 60° C. in an oil bath for 1 hour. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was adjusted to about pH 7 with aqueous sodium hydroxide solution (10 mol/L) and concentrated under reduced pressure to evaporate ethanol. The residue was adjusted to pH 10 with aqueous sodium hydroxide solution (10 mol/L), extracted with dichloromethane (20 ml×3). The combined organic extracts were washed with saturated brine (20 ml), dried over anhydrous magnesium sulfate, filtered to remove the drying agent and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound 3-methyl-5-(2-piperidin-1-yl-ethyl)-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-one 32c (395 m, yield 57%) as a white solid.

1. additionUpon completion of the addition
2. customthe ice-water bath was removed
3. stirringthe reaction mixture was stirred at 60° C. in an oil bath for 1 hour
4. concentrationconcentrated under reduced pressure
5. customto evaporate ethanol
6. extractionextracted with dichloromethane (20 ml×3)
7. washThe combined organic extracts were washed with saturated brine (20 ml)
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationfiltered
10. customto remove the drying agent
11. concentrationconcentrated under reduced pressure
12. customThe residue was purified by silica gel column chromatography