反应详情

温度

0 °C

3(R,S)-[2(R)-(tert-Butyloxycarbonyl)amino-3-phenylpropionylamino]- 5-cyclohexyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (12.7 g, 24.5 mmol) [Example 27, Step 2] was dissolved in ethyl acetate (20 ml) and cooled to 0° C. This solution was then saturated with hydrogen chloride gas. After 1.5 h the resulting precipitate was collected by filtration. After recrystallisation twice from ethanol, the precipitate was partitioned between ethyl acetate (50 ml) and 10% sodium carbonate solution (50 ml). The organic phase was separated and the aqueous extracted with further ethyl acetate (2×50 ml). The combined organic phases were dried (Na2SO4) and evaporated in vacuo to afford the title compound (2 g, 20%) as a pale yellow solid. mp 75°-78° C. 1H NMR (360 MHz, CDCl3) δ 1.03-1.41 (4H, m), 1.48-1.72 (4H, m), 1.82-1.92 (1H, m), 1.97-2.06 (1H, m), 2.70-2.84 (2H, m), 3.28-3.42 (4H, m), 3.76-3.82 (1H, m), 5.36 (1H, d, J=8.2 Hz), 7.21-7.33 (7H, m), 7.50 (1H, t, J=8.4 Hz), 7.56 (1H, d, J=8.1 Hz), 8.67-8.72 (1H, m). [α]D -13.5° (c=0.63, CH3OH).

1. filtrationAfter 1.5 h the resulting precipitate was collected by filtration
2. customAfter recrystallisation twice from ethanol
3. customthe precipitate was partitioned between ethyl acetate (50 ml) and 10% sodium carbonate solution (50 ml)
4. customThe organic phase was separated
5. extractionthe aqueous extracted with further ethyl acetate (2×50 ml)
6. dry with materialThe combined organic phases were dried (Na2SO4)
7. customevaporated in vacuo