The Grignard condensation of methyl imidazole-4-carboxyate (I) with 2,3-dimethylphenylmagnesium bromide (II) in THF gives 4-(2,3-dimethylbenzoyl) imidazole (III), which (without isolation) is submitted to a new Grignard condensation with methylmagnesium iodide (IV) in the same solvent to yield 1-(4-imidazolyl)-1-(2,3-dimethylphenyl)ethanol (V). The dehydration of (V) with potassium hydrogen sulfate at 136 C affords 1-(4-imidazolyl)-1-(2,3-dimethyl-phenyl)ethylene (VI), which is finally hydrogenated with H2 over Pd/C in 2N HCl.
A new synthesis for medetomidine has been reported: The silylation of N,N-dimethylimidazole-1-sulfonamide (I) with tert-butyldimethylsilyl chloride and butyllithium in THF gives the 2-silyl derivative (II), which is acylated with 2,3-dimethylbenzoyl chloride (III) by means of butyllithium in THF, yielding 2-(tert-butyldimethylsilyl)-5-(2,3-dimethylbenzoyl)-N,N-dimethylimidazo le-1-sulfonamide (IV). Hydrolysis of (IV) with refluxing aqueous HCl affords 5-(2,3-dimethylbenzoyl)imidazole (V), which is finally methylated with methyllithium in THF and reduced with Li in liquid NH3.