Trimethylaluminum → 5-(2-Diethylamino-ethyl)-3-methyl-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carboxylic acid tert-butyl ester

5-[3-(2-Diethylamino-ethylamino)-propyl]-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester 1 h (3.547 g, 8.67 mmol) was dissolved in 70 ml of toluene and stirred for 10 minutes at room temperature under an argon atmosphere. The mixture was added with a solution of trimethyl aluminum in toluene (5.6 ml, 2 mol/L, 11.27 mmol), and stirred for another 30 minutes at room temperature until no white smoke was released. The reaction mixture was heated to reflux for 4 hours in an oil bath. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was naturally cooled down to room temperature, quenched with ethanol (10 ml, 95%), and added with anhydrous ethanol (60 ml). The resulting mixture was filtered through a pad of Celite, washed with anhydrous ethanol (200 ml×4) and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound 5-(2-diethylamino-ethyl)-3-methyl-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carboxylic acid tert-butyl ester 1i (0.413 g, yield 75.7%) as a white solid.

1. stirringstirred for another 30 minutes at room temperature until no white smoke
2. temperatureThe reaction mixture was heated
3. temperatureto reflux for 4 hours in an oil bath
4. temperaturethe reaction mixture was naturally cooled down to room temperature
5. customquenched with ethanol (10 ml, 95%)
6. additionadded with anhydrous ethanol (60 ml)
7. filtrationThe resulting mixture was filtered through a pad of Celite
8. washwashed with anhydrous ethanol (200 ml×4)
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by silica gel column chromatography

ORD-Eintrag

ord-c1a0d5e12eda453e842254470f47ad08

Quelldatensatz

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08329682B2