公开(公告)号：EP2504298A4

公开(公告)日：2013-05-01

申请号：EP09851564

申请日：2009-11-26

申请人： HOVIONE CHINA HOLDING LTD

发明人： HU ZHIQI ,  ZHANG HUOYING

IPC分类号： C07B63/00 ,  B01D15/08 ,  C07C231/24 ,  C07C237/46

CPC分类号： C07C231/24 ,  C07B63/00 ,  C07C237/46

摘要： An improved synthesis method for preparation of iodixanol, and a purification process through macroporous adsorption resin chromatographic column and recrystallization are provided. The synthesis method relates to dimerization of 5-acetamido-N,N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-isophthalamide (compound A) to prepare iodixanol, wherein excessive side reactions such as alkylation are effectively inhibited by controlling the pH of the reaction mixture with a boron-containing acidic substance or salts thereof such as boric acid. In this way, the conversion rate of compound A to iodixanol is 85-90%. The iodixanol crude product is purified by a macroporous adsorption resin chromatographic column, obtaining iodixanol product with recovery of 90-95% and purity of 96-98%. The iodixanol crude product is recrystallized in mixed solvent containing 2-methoxyethanol, obtaining iodixanol product with recovery of 90-95% and purity of greater than 99%.