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 2-bromomethyl-benzothiazole (0.63 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 7.5-8.0 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 (50 ml), dried over magnesium sulfate, filtered and concentrated in vacuo to afford (3RS)-1-(benzothiazol-2 -yl)methyl-2,3-dihydro-5-(2-fluorophenyl)-3-phthalimido-1H-1,4-benzodiazepin-2-one. This product was allowed to use in a next reaction step without further purification.

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 (50 ml)
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo