Dimethylformamide → (+)-(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

Participants

Reaction Conditions

Reaction Steps

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-dimethylformarnide 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, water 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 4methyl-2-pentanone. The product was filtered off and converted into the (S)-7,7dimethyl-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=+28.410° (conc.=1% in ethanol) (interm. 5).

Provenance & Evidence