反应详情

温度

80 °C

To a heterogeneous solution of cyclic cidofovir (39 g, 0.131 mol., 1 equiv, purchased from Gilead Sciences) in N,N-DMF (2.0 L) under a nitrogen atmosphere was added N,N′-dicyclohexyl-4-morpholinecarboxamidine (DCMC) (0.131 mol, 38.51 g, 1 equiv.). This was stirred overnight. This dissolved most of the solid in the reaction mixture. To this solution was added 1-bromo-3-hexadecyloxypropane (238.45 g, 0.656 mol, 5 equiv.). The reaction mixture was heated to 80° C. and stirred for 6 hours. The crude reaction mixture was concentrated in vacuo at 80° C. The crude reaction mixture was absorbed on silica gel (300 g) and purified via column chromatography (800 g SiO2). The column was eluted with dichloromethane (6 L) to remove the excess 1-bromo-3-hexadecyloxypropane. The solvent phase was then switched to 9:1 CH2Cl2:EtOH (32 L). The product came off with this solvent system. Fractions 30-39 were combined to give hexadecyloxypropyl-cyclic cidofovir (17.8 g) in a 25% yield.

1. dissolutionThis dissolved most of the solid in the reaction mixture
2. stirringstirred for 6 hours
3. customThe crude reaction mixture
4. concentrationwas concentrated in vacuo at 80° C
5. customThe crude reaction mixture
6. customwas absorbed on silica gel (300 g)
7. custompurified via column chromatography (800 g SiO2)
8. washThe column was eluted with dichloromethane (6 L)
9. customto remove the excess 1-bromo-3-hexadecyloxypropane