反应详情

温度

30 °C

The mixture of (±)-[2R*[1S*,5S*(S*)]]-α,α′-[phenylmethyliminobis (methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] (48 gm), acetic acid (480 gm) and 5% palladium on charcoal (19 gm) was taken into a hydrogenation flask and subjected to hydrogenation under a hydrogen gas pressure of 1.5 kg/cm2 for 3 hours at 25-40° C. Then the reaction mixture was filtered on hi-flo and washed with acetic acid (55 gm). The solvent was distilled off completely under reduced pressure and then co-distilled twice with ethyl acetate (each time 60 ml). To the resulting mass, ethyl acetate (480 ml) was added, refluxed for 1 hour and then cooled to 25-35° C. The reaction mass was stirred for 4 hours, again cooled to 0-10° C. and stirred for 1 hour 30 minutes. Filtered the material and washed with ethyl acetate (60 ml). The resulting wet cake was stirred with methanol (850 ml) and 25% monomethyl amine (60 ml) for 1 hour at 25-35° C., cooled to 0-10° C. and then stirred for 1 hour at 0-10° C. Filtered the material and washed with methanol (60 ml) to give 40.5 gm of (±)-[2R*[1S*,5S*(S*)]]-α,α′-[iminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] (Nebivolol) (HPLC purity: 99.2%).

1. customwas taken into a hydrogenation flask
2. customfor 3 hours
3. customat 25-40° C
4. filtrationThen the reaction mixture was filtered on hi-flo
5. washwashed with acetic acid (55 gm)
6. distillationThe solvent was distilled off completely under reduced pressure
7. additionTo the resulting mass, ethyl acetate (480 ml) was added
8. temperaturerefluxed for 1 hour
9. temperatureagain cooled to 0-10° C.
10. stirringstirred for 1 hour 30 minutes
11. filtrationFiltered the material
12. washwashed with ethyl acetate (60 ml)
13. stirringThe resulting wet cake was stirred with methanol (850 ml) and 25% monomethyl amine (60 ml) for 1 hour at 25-35° C.
14. temperaturecooled to 0-10° C.
15. stirringstirred for 1 hour at 0-10° C
16. filtrationFiltered the material
17. washwashed with methanol (60 ml)