反应详情

A mixture of 29.4 g 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) (intermediate (5)), 2.0 g of sodium sulfite and 151 ml of a hydrobromic acid solution 48% in water was stirred for 5 hours at reflux temperature. The reaction mixture was cooled to room temperature and water was added. The whole was neutralized with potassium carbonate to pH 7 while stirring in a mixture of dichloromethane and 1-butanol (90:10 by volume). The separated organic layer was dried, filtered and evaporated in vacuo. The residue was triturated in methanol. The precipitated product was filtered off and purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (98:2 by volume) 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 dried, yielding 10.4 g (77.7%) of (+)-(S)-2,4-dihydro-4-[4-[4-(4-hydroxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one; mp. 1 80.6° C.; [α]D20=+4.38° (conc.=1% in methanol) (interm. 7).

1. temperatureat reflux temperature
2. customThe separated organic layer was dried
3. filtrationfiltered
4. customevaporated in vacuo
5. customThe residue was triturated in methanol
6. filtrationThe precipitated product was filtered off
7. custompurified by column chromatography over silica gel using
8. additiona mixture of trichloromethane and methanol (98:2 by volume) as eluent
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. customdried