反应详情

3-Methyl-5-(2-morpholin-4-yl-ethyl)-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carboxylic acid tert-butyl ester 10b (725 mg, 1.92 mmol) was dissolved in trifluoroacetic acid (2.6 ml, 34.2 mmol) in an ice-water bath under stirring. The reaction mixture was stirred at 40° C. in a water bath for 5 minutes, added with triethoxy methane (0.42 ml, 2.5 mmol) in one portion at −5° C. in an ice-water bath, and stirred for 2 minutes. Then the ice-salt bath was removed, and the reaction mixture was allowed to warm up to room temperature, became brown and stirred for another 2 hours. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was quenched with a little water, adjusted to pH 8 with dilute sodium hydroxide solution (2 mol/L) and extracted with dichloromethane (50 ml×3). The combined organic extracts were concentrated under reduced pressure to obtain henna solid. The solid was purified by silica gel column chromatography to obtain the title compound 3-methyl-5-(2-morpholin-4-yl-ethyl)-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehyde 10c (240 mg, yield 40%) as a light yellow solid.

1. stirringThe reaction mixture was stirred at 40° C. in a water bath for 5 minutes
2. stirringstirred for 2 minutes
3. customThen the ice-salt bath was removed
4. stirringstirred for another 2 hours
5. customthe reaction mixture was quenched with a little water
6. extractionextracted with dichloromethane (50 ml×3)
7. concentrationThe combined organic extracts were concentrated under reduced pressure
8. customto obtain henna solid
9. customThe solid was purified by silica gel column chromatography