反应详情

To a suspension of sodium hydride (0.065 g of a 65% dispersion in mineral oil) in dry N,N-dimethylformamide (5 ml) was added dropwise a solution of (3RS)-3-tert-butoxycarbonylamino-2,3-dihydro-5-isopropyl-1H-1, 4-benzodiazepin-2-one (0.508 g) in dry N,N-dimethylformamide (5 ml) under cooling in an ice-bath. The mixture was stirred under the same condition for 30 minutes and then at ambient temperature for 2 hours. To the mixture was added dropwise a solution of 2-acetyl-3-bromomethylthiophene (0.420 g) in dry N,N-dimethylformamide under cooling in an ice-bath. After completion of the addition, the mixture was stirred under the same condition for 30 minutes and then at ambient temperature overnight. The resultant mixture was concentrated in vacuo. The residue was treated with ethyl acetate (100 ml), washed with water (50 ml) and dried over anhydrous sodium sulfate. Filtration and evaporation gave a crude product. The product was purified by column chromatography on silica gel with an eluent of a mixture of chloroform and ethyl acetate (10: 1) to give (3RS)-1-(2-acetylthiophen-3-yl)methyl-3-tert-butoxycarbonylamino-2,3-dihydro-5-isopropyl-1H-1,4-benzodiazepin-2-one (0.380 g).

1. temperatureunder cooling in an ice-bath
2. waitat ambient temperature for 2 hours
3. temperatureunder cooling in an ice-bath
4. additionAfter completion of the addition
5. stirringthe mixture was stirred under the same condition for 30 minutes
6. customat ambient temperature
7. customovernight
8. concentrationThe resultant mixture was concentrated in vacuo
9. additionThe residue was treated with ethyl acetate (100 ml)
10. washwashed with water (50 ml)
11. dry with materialdried over anhydrous sodium sulfate
12. filtrationFiltration and evaporation
13. customgave a crude product
14. customThe product was purified by column chromatography on silica gel with an eluent of a mixture of chloroform and ethyl acetate (10: 1)