反应详情

To a suspension of sodium hydride (0.119 g of a 60% dispersion in mineral oil) in dry N,N-dimethylformamide (8 ml) was added dropwise a solution of (3RS)-3-tert-butoxycarbonylamino-2,3-dihydro-5- (2-fluorophenyl)-1H-1,4-benzodiazepin-2-one (1.005 g) in dry N,N-dimethylformamide (5 ml) under stirring at cooling in an ice-bath. The mixture was stirred at the same temperature for 30 minutes and then at room temperature for 1.5 hours. To the mixture was added a solution of 2-acetyl-3-bromomethylthiophen (0.82 g) in N,N-dimethylformamide (3 ml) under cooling in an ice-bath. The mixture was stirred under the same condition for 30 minutes and then at ambient temperature overnignt. The reaction mixture was concentrated in vacuo. The residue was treated with ethyl acetate and water. The organic layer seas washed with water and a brine, and dried over sodium sulfate. Removal of the solvent at reduced pressure gave a crude product. The crude product was purified by column chromatography on silica gel with chloroform as an eluent to give (3RS)-1-(2-acetylthiophen-3-yl)methyl-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-one (0.80 g).

1. temperatureat cooling in an ice-bath
2. stirringThe mixture was stirred at the same temperature for 30 minutes
3. temperatureunder cooling in an ice-bath
4. stirringThe mixture was stirred under the same condition for 30 minutes
5. customat ambient temperature
6. concentrationThe reaction mixture was concentrated in vacuo
7. additionThe residue was treated with ethyl acetate and water
8. washThe organic layer seas washed with water
9. dry with materiala brine, and dried over sodium sulfate
10. customRemoval of the solvent at reduced pressure
11. customgave a crude product
12. customThe crude product was purified by column chromatography on silica gel with chloroform as an eluent