反应详情

To a solution of 1-(4-morpholinecarbonyl)-1,4-diazepane hydrochloride (50 g, 0.2 mol) and triethylamine (42 ml, 30.5 g, 0.3 mol) in dichloromethane (400 ml) at 5° C. was added acetic anhydride (23 ml, 24.9 g, 0.24 mol) dropwise over 15 minutes and the reaction was then stirred for a further 2 hours at room temperature under nitrogen. Dilution with dichloromethane (600 ml) was followed by washing with saturated aqueous sodium bicarbonate (2×200 ml) and the combined aqueous layers extracted with dichloromethane (1×100 ml). The dichloromethane layers were combined and washed with saturated brine, dried over MgSO4 and evaporated to give a light brown oil. This was dissolved in dichloromethane (300 ml) and treated with triethylamine (8 ml, 5.8 g, 0.06 mol) and ethanol (5 ml), stirred for 1 hour at room temperature then washed with saturated sodium bicarbonate and the aqueous layer extracted with dichloromethane (5×). The combined dichloromethane layers were dried over MgSO4 and evaporated under reduced pressure to give a yellow oil which was then azeotroped with dichloromethane (4×) to give the title compound as a yellow oil (47.1 g, 92%). Rf 0.45 (0.880 aqueous ammonia: methanol:dichloromethane 1:10:90, v/v). MS m/z 256 (MH)+. Found: C,52.62; H,8.18; N,15.02; C12H21N3O3 0.3CH2Cl2 requires C, 52.61; H, 7.75; N,14.96%.

1. washby washing with saturated aqueous sodium bicarbonate (2×200 ml)
2. extractionthe combined aqueous layers extracted with dichloromethane (1×100 ml)
3. washwashed with saturated brine
4. dry with materialdried over MgSO4
5. customevaporated
6. customto give a light brown oil
7. stirringstirred for 1 hour at room temperature
8. washthen washed with saturated sodium bicarbonate
9. extractionthe aqueous layer extracted with dichloromethane (5×)
10. dry with materialThe combined dichloromethane layers were dried over MgSO4
11. customevaporated under reduced pressure
12. customto give a yellow oil which
13. customwas then azeotroped with dichloromethane (4×)