反应详情

3-Methyl-5-[3-(2-pyrrolidin-1-yl-ethylamino)-propyl]-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester 28a (6.754 g, 16.6 mmol) was dissolved in 150 ml of toluene under stirring, and added slowly with a solution of trimethyl aluminum in toluene (16.6 ml, 2 mol/L, 33.2 mmol) to the solution under an argon atmosphere. The reaction mixture was stirred for 20 minutes at room temperature until no white smoke was released, and refluxed for another 3.5 hours in an oil bath. After thin lay chromatography showed the disappearance of starting materials, the oil bath was removed. The reaction mixture was quenched with little ethanol (95%), added with ethyl acetate (100 ml), filtered through a pad of Celite and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound 3-methyl-4-oxo-5-(2-pyrrolidin-1-yl-ethyl)-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carboxylic acid tert-butyl ester 28b (3.894 g, yield 65%) as a yellow oil.

1. stirringThe reaction mixture was stirred for 20 minutes at room temperature until no white smoke
2. temperaturerefluxed for another 3.5 hours in an oil bath
3. customthe oil bath was removed
4. customThe reaction mixture was quenched with little ethanol (95%)
5. additionadded with ethyl acetate (100 ml)
6. filtrationfiltered through a pad of Celite
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by silica gel column chromatography