反应详情

To a suspension of sodium hydride (0.123 g of a 65% dispersion in mineral oil) in dry N, N-dimethylformamide (10 ml) was added dropwise a solution of (3RS)-3-benzyloxycarbonylamino-2,3-dihydro-5-isopropyl-1H-1,4-benzodiazepin-2-one (1.00 g) in dry N,N-dimethylformamide (5 ml) under cooling in an ice-bath. The mixture was stirred at the same temperature for 1 hour and then at room temperature for 1 hour. To the mixture was added dropwise a solution of N-bromomethylcarbonyl-3-azabicyclo[3.2.2]nonane (0.77 g) in dry N,N-dimethylformamide (5 ml) and stirred at the same condition for 2 hours. The reaction mixture was concentrated in vacuo and the residue was taken up with ethyl acetate (100 ml) and a saturated aqueous sodium hydrogen carbonate (100 ml). The organic layer was washed with a brine (50 ml) and dried over anhydrous magnesium sulfate. Filtration and evaporation gave (3RS)-1-[(3-azabicyclo[3.2.2]non-3-yl)carbonylmethyl]-3-benzyloxy-carbonylamino-2,3-dihydro-5-isopropyl-1H-1,4-benzodiazepin-2-one.

1. temperatureunder cooling in an ice-bath
2. waitat room temperature for 1 hour
3. stirringstirred at the same condition for 2 hours
4. concentrationThe reaction mixture was concentrated in vacuo
5. washThe organic layer was washed with a brine (50 ml)
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationFiltration and evaporation