合成路线1

The synthesis of erbulozole, starting from 1-(4-methoxyphenyl)-2-(1H-imidazol-1-yl)ethanone (I) is outlined. Ketalization of (I) with glycerin (II) was performed in n-heptane with p-toluenesulfonic acid as the catalyst and under azeotropic removal of H2O. The resulting dioxolane derivative (III), arising as a cis-trans mixture, was benzoylated to the ester (IV). Cis-trans isomers were separated by column chromatography over silica gel (Merck, Silica gel 60), using a mixture of trichloromethane and methanol (98:2 by volume) as the eluent. Saponification of the cis-benzoate (V) with sodium hydroxide in dioxane-water medium at room temperature afforded the alcohol (VI), which was converted to the methanesulfonate (VII) with methanesulfonylchloride in dry pyridine and methylenechloride (1:1 by volume). Under a nitrogen atmosphere, compound (VII) was coupled with (VIII) in acetone using K2CO3 as an acid acceptor to the target compound, erbulozole.