碘海醇、碘克沙醇中间体水解物的合成工艺改进
摘要
对碘海醇、碘克沙醇的中间体水解物(1)的合成工艺进行改进。以5-氨基-N,N′-双(2,3-二羟丙基)-2,4,6-三碘-1,3-苯二甲酰胺(2)作原料,采用醋酐在盐酸催化下得到酰化中间体(3)。之后在甲醇/盐酸体系中选择性水解反应得到产物(1)。该工艺路线反应条件简单、易于操作、副反应少、成本低,适合工业化生产,总收率89.8%。
The synthesis of intermediate of iohexol and iodixanol hydrolysate(1) was improved. The material 5-Amino-N, N '-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-phthalamide(2) was acetylated by acetic anhydride with HCl as catalyst, and acetylate intermediate(3) was obtained. Then, the acetyl groups were removed selectively under MeOH/HCl condition, and product(1) yielded.The improved process is simpler in reaction condition, easier to operate, less by-products, less cost, and more suitable for scale up.The overall yield was 89.8%.
The synthesis of intermediate of iohexol and iodixanol hydrolysate(1) was improved. The material 5-Amino-N, N '-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-phthalamide(2) was acetylated by acetic anhydride with HCl as catalyst, and acetylate intermediate(3) was obtained. Then, the acetyl groups were removed selectively under MeOH/HCl condition, and product(1) yielded.The improved process is simpler in reaction condition, easier to operate, less by-products, less cost, and more suitable for scale up.The overall yield was 89.8%.
引文
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[4]孙跃军,郑国钧.碘海醇的合成工艺优化[J].化学试剂,2012,34(2):185-186.
[5]罗世能,谢敏浩,奚月芬,等.非离子型X-CT造影剂碘海醇的合成[J].中国医药工业杂志,1995,26(10):433-435.
[6]罗世能,沈永嘉,谢敏浩,等.碘海醇的合成工艺改进[J].中国医药工业杂志,2003,34(6):261-262.
[2]吴恩惠.介绍经肾排泄水溶性碘造影剂[J].中华放射学杂志,1992,26(2):131-132.
[3]孙立军,李敬邦,毛松寿.安射力在选择性冠状动脉及心室造影中的初步应用[J].实用放射学杂志,1997,13(10):609-611.
[4]孙跃军,郑国钧.碘海醇的合成工艺优化[J].化学试剂,2012,34(2):185-186.
[5]罗世能,谢敏浩,奚月芬,等.非离子型X-CT造影剂碘海醇的合成[J].中国医药工业杂志,1995,26(10):433-435.
[6]罗世能,沈永嘉,谢敏浩,等.碘海醇的合成工艺改进[J].中国医药工业杂志,2003,34(6):261-262.