头孢唑兰活性酯合成工艺改进

摘要

Improvement in the synthesis of 2-(5-Amino-1,2,4-thiadiazol-3-yl) -2-(z) -methoxyimino acetic acide 2-benzo-thiazolyl thioester was studied in the condition of mixed solvent and substitution of triethyl phosphate by triphenylphosphine as condensation catalyst.By orthogonal test, the influence of solvents, temperature and time on the yield and quality of active ester was researched.An improved procedure is established: when n ( 2-(5-Amino-l, 2,4-thiadiazol-3-yl ) -2-( z ) -methoxyimino acetic acide ): n ( DM ): n ( triethyl phosphate) equals 1: 1.1: 1.2, V(dichloromethane): V(acetonitrile) = 1: 1, the product is obtained through four hours at 25 ℃ with a yield of 94.8％.The measured purity of the product is 99.2％.%在混合溶剂条件下,以亚磷酸三乙酯替代三苯基磷做缩合催化剂,改进头孢唑兰活性酯的合成工艺.经正交实验,考察溶剂、温度和时间等因素对活性酯收率和质量的影响,确定最佳工艺条件为:n(氨噻二唑肟乙酸):n(二硫化二苯并噻唑):n(亚磷酸三乙酯)=1:1.1:1.2,V(二氯甲烷):V(乙腈)=1:1,反应温度为25 ℃,反应时间4 h.在此条件下,产品收率可达94.8%,HPLC测定纯度为99.2%.