rac N-Benzyl Nebivolol → Nebivolol
反応式
C1(C[N:8]([CH2:23][CH:24]([CH:26]2[CH2:31][CH2:30][C:29]3[CH:32]=[C:33]([F:36])[CH:34]=[CH:35][C:28]=3[O:27]2)[OH:25])[CH2:9][CH:10]([CH:12]2[CH2:17][CH2:16][C:15]3[CH:18]=[C:19]([F:22])[CH:20]=[CH:21][C:14]=3[O:13]2)[OH:11])C=CC=CC=1>[Pd].C(O)(=O)C>[NH:8]([CH2:23][CH:24]([CH:26]1[CH2:31][CH2:30][C:29]2[CH:32]=[C:33]([F:36])[CH:34]=[CH:35][C:28]=2[O:27]1)[OH:25])[CH2:9][CH:10]([CH:12]1[CH2:17][CH2:16][C:15]2[CH:18]=[C:19]([F:22])[CH:20]=[CH:21][C:14]=2[O:13]1)[OH:11]参加物
4
反応条件
- 温度
- 30 °C
実験手順
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%).