头孢曲松钠的合成工艺改进
An improvement for synthesis of ceftriaxone sodium
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摘要: 研究头孢曲松钠的合成新工艺。以7-氨基头孢烷酸(7-ACA)与2，5-二氢-6-羟基-2-甲基-3-巯基-5-氧-1，2，4-三嗪(TTZ)在三氟化硼/乙腈作用下缩合，反应生成的7-氨基-3-［(2，5-二氢-6-羟基-2-甲基-5-氧代-1，2，4-三嗪-3-巯基)甲基］-3-头孢-4-羧酸(7-ACT)与2-(2-氨基-4-噻唑基)-2-(甲氧亚氨基)乙酸硫代苯并噻唑酯(AE)在三乙胺的催化下反应生成头孢曲松和2-巯基苯并噻唑(M)，过滤，除去M固体，滤液用醋酸钠处理得到头孢曲松钠。本工艺无需从母液中单独回收M，溶剂消耗明显减少，无二次环境污染，操作简单，已成功用于工业化生产。Abstract: To develop new synthetic process of ceftriaxone sodium, 7-amino-3-［(2, 5-dihydro-6-hydroxy-2-methyl-5-oxo-1, 2, 4-triazin-3-yl)thiomethyl］-3-cephem-4-carboxylic acid(7-ACT)was synthesized from 7-aminocephalosporanicacid(7-ACA)by reaction with 2, 5-dihydro-6-hydroxy-2-methyl-3-mercapto-5-oxo-1, 2, 4-triazine(TTZ)under the catalysis of BF3/C2H3N. Ceftriaxone was prepared from 7-ACT by condensation with 2-(2-amino-4-thiazolyl)-2-methoxyiminoacetic thiobenzothiazole ester(AE)using triethylamine as catalyst. After removing the by-product 2-mercaptobenzothiazole(M)through filtration, the filtrate was treated with sodium acetate to give ceftriaxone sodium. This improved process eliminates the working procedure for separating compound M from the mother liquor, and has the advantages of less solvent consumption and convenient operation, and has been successfully used in commercial production.
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Keywords:
- ceftriaxone sodium /
- antibiotics /
- synthesis /
- process improvement
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