Prodn. of 4-(4'-ortho-chloro-phenyl)-4-oxo-2-methylene butyric acid - or itanoxone, by acylation of 2-chloro-bi:phenyl with itaconic animoride in 1,2-di:chloroethane

摘要

In an industrial-scale prodn. process for itanoxone (I) (4-(4'-orthochlorophenyl) 4-oxo-2-methylene butyric acid), 2- chlorobiphenyl (II) is acylated by itaconic anhydride (III) in the presence of AlCl3: The reaction is carried out in 1,2- dichloroethane (IV) as solvent, then crystallisation is performed by addn. of acetone or alcohol to facilitate filtration. After recrystallisation from dioxan or DMF-water, the prod. is treated to make possible the removal of residual organic solvents. Specifically, solvent residues which cannot be removed by thermal treatment or washing are removed by dissolving the (I) in water, in the form of a salt, pref. by dissolving in water in the form of a salt, pref. by dissolving in a cold soln. of an organic or mineral base (esp. soda) at a pH of less than 9.5. (I) of pharmaceutical quality can be prepd. e.g. by neutralising the aq. soln. of (I) with conc. acid soln.