反应详情

温度

80 °C

A mixture of 3.5 g of (2,4-dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]-phenyl]-3H-1,2,4-triazol-3-one, 0.6 g of a sodium hydride dispersion 50% and 100 ml of N,N-dimethylformamide was stirred for 3 hours at 80° C. After the addition of 3.5 g of (R)-2-butanol 4-bromobenzenesulfonate (ester) (intermediate (3)), stirring was continued for 6 hours at this temperature. After cooling, waster was added. The crystallized product was filtered off and taken up in trichloromethane. The undissolved part was filtered off. The remaining solution was dried and purified by column chromatography over silica gel using trichloromethane as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 4-methyl-2-pentanone. The product was filtered off and converted into the (S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptane-1-methanesulfonate salt in 2-propanone. The salt was filtered off and recrystallized from 1-butanol. The product was filtered off and dried, yielding 1.2 g (13.7%) of (+)-(S)-2,4-dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]-phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one (S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptane-1-methanesulfonate (1:2); mp. 192.0° C.; [α]D20 =+28.41° (conc.=1% in ethanol) (interm. 5).

1. stirringstirring
2. waitwas continued for 6 hours at this temperature
3. temperatureAfter cooling
4. additionwaster was added
5. filtrationThe crystallized product was filtered off
6. filtrationThe undissolved part was filtered off
7. customThe remaining solution was dried
8. custompurified by column chromatography over silica gel
9. customThe pure fractions were collected
10. customthe eluent was evaporated
11. customThe residue was crystallized from 4-methyl-2-pentanone
12. filtrationThe product was filtered off
13. filtrationThe salt was filtered off
14. customrecrystallized from 1-butanol
15. filtrationThe product was filtered off
16. customdried