Synthesis of the methanesulfonates of alpha-(4-chlorophenyl)-alpha-[1-(2-chlorophenyl)ethenyl]-1H-1,2,4-triazole -1-ethanol and alpha-[1-(2-chlorophenyl)ethenyl]-alpha-(2,4-difluorophenyl)-1H-1,2,4-tria zole-1-ethanol, alpha styryl carbinol antifunga

摘要

The methanesulfonates of (alpha-(4-chlorophenyl)-alpha-[1-(2-chlorophenyl)ethenyl]-1H-1,2,4-triazol e-1-ethanol and alpha-[1-(2-chlorophenyl)ethenyl]-alpha-(2,4-difluorophenyl)-1H-1,2,4-tria zole-1-ethanol (la,b) are orally effective alpha-styryl carbinol derivatives developed for the treatment and prevention of systemic fungal infections. Practical new processes amenable for the large-scale production of these compounds are described. Of note is the selection of dichlorostyrene as a convenient precursor of the styryl portion, modification of a sensitive Grignard addition into a realistic preparative reaction and the use of 1,2,4-triazole simultaneously as a base transfer agent and nucleophile. [References: 34]