反应详情

To a suspension of sodium hydride (0.11 g of a 60% dispersion in mineral oil) in N,N-dimethylformamide (20 ml) was added gradually (3RS)-2,3-dihydro-5-(2-fluorophenyl)-3-phthalimido-1H-1,4-benzodiazepin-2-one (1.00 g) under nitrogen atmosphere at cooling in an ice-bath. The mixture was stirred under the same condition for 0.5 hour and at ambient temperature for 1 hour. The mixture was cooled in an ice-bath and a solution of 6-bromomethyl coumarin (0.66 g) in N,N-dimethylformamide (5 ml) was added dropwise thereto. The mixture was stirred for 1 hour at the same temperature and at ambient temperature overnight. To the reaction mixture was added acetic acid (0.5 g) under cooling in an ice-bath. The resultant mixture was poured into a mixture of ethyl acetate (100 ml) and water (50 ml) under stirring. The mixture was adjusted to pH 7.5 with sodium bicarbonate. The organic layer was separated. The aqueous layer was extracted with ethyl acetate (50 ml). The combined organic layer was washed with a brine (30 ml), dried over magnesium sulfate, filtered and concentrated in vacuo to afford a crude product. The crude product was purified by column chromatography on silica gel (eluent : CHCL3) to afford (3RS)-2,3-dihydro-5-(2-fluorophenyl)-1-(2-oxo-2H-1-benzopyran-6-yl)methyl-3-phthalimido-1H-1,4-benzodiazepin-2-one as a colorless crystalline solid (1.30 g).

1. temperatureat cooling in an ice-bath
2. temperatureThe mixture was cooled in an ice-bath
3. stirringThe mixture was stirred for 1 hour at the same temperature and at ambient temperature overnight
4. temperatureunder cooling in an ice-bath
5. stirringunder stirring
6. customThe organic layer was separated
7. extractionThe aqueous layer was extracted with ethyl acetate (50 ml)
8. washThe combined organic layer was washed with a brine (30 ml)
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customto afford a crude product
13. customThe crude product was purified by column chromatography on silica gel (eluent : CHCL3)