艾瑞昔布的合成

发布时间：2018-05-06 12:28

本文选题：艾瑞昔布 + 非甾体抗炎药　；参考：《中国医药工业杂志》2017年04期

【摘要】：本研究提供了一条经济、绿色、适合工业化生产的工艺路线合成1.1类非甾体抗炎镇痛药艾瑞昔布(1)。以2-[4-(甲基磺酰基)苯基]环氧乙烷(2)为起始原料,经加成开环生成N-正丙基-?-羟基-4-甲磺酰基苯乙胺(3);3与4-甲基苯乙酸在缩合剂羰基二咪唑作用下经酸胺缩合生成N-正丙基-N-[2-羟基-2-(4-甲磺酰基苯基)]乙基-4-甲基苯乙酰胺(4),操作简便,收率98%;4经Jone's试剂氧化后,在碳酸钾/乙醇/水体系中(替换文献的叔丁醇钾/叔丁醇体系)环合得1,反应时间从8 h缩短至2 h,收率从61%提高至78%,同时简化了后处理,改善了产品外观。总收率38.5%(以2计),较文献提高了12%。
[Abstract]:This study provides an economical, green and suitable industrial route for the synthesis of class 1.1 nonsteroidal anti-inflammatory analgesics. Starting with 2- [4-( methyl sulfonyl) phenyl] ethylene oxide 2), Synthesis of N-n-propyl-4-methylsulfonyl phenylethylamine (N- n-propyl-4-methylsulfonyl phenyl)] ethyl-4-methylphenylethylamine via acid-amine condensation with 4-methylphenylacetic acid in the presence of carbonyl diimidazole by adding ring opening to form N- n-propyl -N- [2-hydroxy-2-N-4-methanesulfonyl phenyl] ethyl-4-methylphenyl Acetamide is simple and easy to operate. After oxidation with Jone's reagent, 1 was synthesized by cyclization in potassium carbonate / ethanol / water system. The reaction time was shortened from 8 h to 2 h, the yield was increased from 61% to 78%, and the reprocessing was simplified. Improved product appearance. The total yield was 38.5%, which was 12% higher than that in the literature.
【作者单位】：江苏恒瑞医药股份有限公司;
【分类号】：R971+.1

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