PROCESS FOR PREPARATION OF IOPAMIDOL Russian patent published in 2018 - IPC C07C231/02 C07F5/02 C07F5/04 

FIELD: chemistry.

SUBSTANCE: invention relates to methods for synthesis of iodine-containing contrast agents, specifically to a method for the preparation of Iopamidol (II), which comprises the following reaction, where X represents OR₂ or R₃ and R₂ and R₃ are C₁-C₆linear or branched alkyl, C₃-C₆cycloalkyl, C₆aryl optionally substituted with a group selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl and phenyl. Method includes steps a)-c). At step a), compound (I) is reacted with an (S)-2-(acetyloxy)propanoyl chloride acylating agent in a reaction medium to obtain the N-(S)-2-(acetyloxy)propanoyl derivative of compound (I). At step b), the intermediate from step a) is hydrolysed with an aqueous solution at a pH of 0 to 7, by adding water or a diluted alkaline solution, releasing hydroxyls from boron-containing protecting groups, obtaining the acetyloxy derivative of compound (II) and optional reduction of the boron derivative. Step c) comprises alkaline hydrolysis of the acetyloxy compound of compound (II), reduction of (S)-2-(hydroxy)propanoyl group to obtain Iopamidol (II). Invention also relates to a process for the preparation of Iopamidol (II) starting from 5-nitroisophthalic acid (5-NIPA), compound of formula (I) and use thereof in the synthesis of Iopamidol (II).

EFFECT: disclosed method enables to carry out the reaction in one reaction vessel and increases the total yield of Iopamidol (II), and also provides the recovery and reuse of the reactant used as the hydroxyl protecting group.

29 cl, 14 ex

щелочной гидролиз - alkaline hydrolysis

йопамидол - Iopamidol