反应详情

A mixture of (±)-2,4-dihydro-4-[4-[4-(4-hydroxyphenyl)-1-piperazinyl]phenyl]-2-(1-methyl-2-oxopropyl)-3H-1,2,4-triazol-3-one (0.05 mol) and (−)-(S)-α-methyl-benzenemethanamine (0.1 mol) in THF (500 ml) was hydrogenated at 50° C. for 48 hours with Pd/C 10% (3 g) as a catalyst in the presence of titanium(VI) n-butoxide (28.4 g) and thiophene solution (3 ml). The catalyst was filtered off. Pd/C 10% (10 g) and thiophene solution (10 ml) were added again. Hydrogenation was continued at 50° C. for 48 hours. After uptake of H2, the catalyst was filtered off and the filtrate was evaporated. The residue was stirred in CH2Cl2, CH3OH and H2O. The mixture was alkalized with NaOH and filtered over dicalite. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was triturated in DIPE, filtered off and dried, yielding 19 g (74%) of [(R*,R*)(S)+(R*,S*)(S)]-2,4-dihydro-4-[4-[4-(4-hydroxyphenyl)-1-piperazinyl]phenyl]-2-[2-[(1-phenylethyl)amino)-1-methylpropyl]-3H-1,2,4-triazol-3-one (interm. 2).

1. filtrationThe catalyst was filtered off
2. additionPd/C 10% (10 g) and thiophene solution (10 ml) were added again
3. filtrationAfter uptake of H2, the catalyst was filtered off
4. customthe filtrate was evaporated
5. filtrationfiltered over dicalite
6. customThe organic layer was separated
7. customdried
8. filtrationfiltered
9. customthe solvent was evaporated
10. customThe residue was triturated in DIPE
11. filtrationfiltered off
12. customdried