反应详情

温度

5 °C

To a solution of (3RS)-3-tert-butoxycarbonylamino-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one (5.88 g) in N,N-(1imethylformamide (100 ml) was added portionwise sodium hydride (60% dispersion in mineral oil, 0.76 g) under stirring and cooling at 5° C. The mixture was stirred under the same condition for 0.5 hour and at ambient temperature for 1 hour. To the mixture was added dropwise a solution of ethyl bromoacetate (3.19 g) in N,N-dimethylformamide (10 ml) under cooling in an ice-bath. After the addition was completed, the mixture was stirred at ambient temperature for 3 hours. The reaction mixture was poured into water (300 ml) under vigorous stirring. The resultant precipitates were collected by filtration, washed with water and dried under reduced pressure over phosphorus pentoxide to afford (3RS)-1-ethoxycarbonylmethyl-3-tert-butoxycarbonylamino-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one (7.25 g) as a crystalline powder, which was used in a following reaction step without further purification.

1. stirringThe mixture was stirred under the same condition for 0.5 hour and at ambient temperature for 1 hour
2. temperatureunder cooling in an ice-bath
3. additionAfter the addition
4. stirringthe mixture was stirred at ambient temperature for 3 hours
5. customThe resultant precipitates
6. filtrationwere collected by filtration
7. washwashed with water
8. dry with materialdried under reduced pressure over phosphorus pentoxide