摘要
研究第三代头孢菌素头孢地嗪钠的适合工业化生产的制备工艺,即7-氨基头孢烷酸(7-ACA)与2-(2-氨基噻唑-4-基)-(顺式)-2-甲氧亚胺乙酰硫代苯并噻唑活性酯(5)在二氯甲烷于5℃反应4h生成头孢噻肟酸(3),收率90%,3在水-丙酮溶液中碳酸钠存在下与2-巯基-4-甲基-5-噻唑乙酸(4)在55～60℃反应4h生成头孢地嗪酸(2),收率66.3%,最后2与异辛酸钠丙酮溶液在低温反应成盐得到头孢地嗪钠(1),收率89.7%.三步反应总收率53.5%.所得产品含量99.5%(HPLC).
An improved process for the large-scale preparation of cefodizime disodium (1), a third (generation) cephalosporin, was synthesized from 7-aminocephalosporanic acid (7-ACA) in three steps. 7-ACA reacted with S-benzothiazol-2-amino-alpha-methoxyimino-4-thiazoleacetate at 5℃ for 4h in CH_2Cl_2 to yield cefatoxime acid (3) (90%). Then cefodizime acid (2) was prepared by the reaction of compound 3 and 2-mercapto-4-methyl-1,3-thiazol-5-yl-acetic acid at 55～60℃ for 4h in acetone-water (66.3%). Finally, compound reacted with sodium 2-ethylhexanoate at 5℃ to yield (1) (89.7%). The title compound was obtained in 53.5% overall yield with high purity [above 99.5% (HPLC)].
出处
《中国抗生素杂志》
CAS
CSCD
北大核心
2005年第6期332-335,共4页
Chinese Journal of Antibiotics
