盐酸莫西沙星的合成工艺研究

Synthesis of Moxifloxacin hydrochloride

以喹啉羧酸乙酯为原料,经过螯合、缩合、酸解成盐、精制三步制备得到盐酸莫西沙星,总收率72.6%,纯度99.96%。运用HRMS和NMR(^(1)H NMR和^(13)C NMR)对中间体和目标产物进行了表征。通过对关键步骤的工艺优化,确定了螯合最佳工艺条件:n(乙酸酐)∶n(硼酸)∶n(喹啉羧酸乙酯)=4.75∶1.4∶1.0,干燥温度为50℃;对缩合、酸解成盐的最佳条件为:以乙腈作为反应溶剂,室温反应4 h,n(三乙胺)∶n(螯合物)=1.0∶1.0,盐酸调pH值为1.0。

1-Cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid ethyl ester(ethyl quinoline carboxylate)was used as the starting material,through chelation,condensation,acid hydrolysis to salt and purification to obtain Moxifloxacin hydrochloride.The total product yield was 72.6%and the purity was 99.96%.The structures of the target products and its intermediates were characterized by HRMS and NMR spectra(^(1)H NMR and^(13)C NMR).Through the process optimization of the key steps,and the optimal process conditions for condensation were determined:n(acetic anhydride)∶n(boracic acid)∶n(ethyl quinoline carboxylate)=4.75∶1.4∶1.0 and the drying temperature is 50℃;the optimal process conditions for acidolysis to salt were determined:acetonitrile as the reaction solvent,reaction at room temperature for 4 h,n(triethylamine)∶n(chelate)=1.0∶1.0,adjusted with hydrochloric acid The pH is 1.0.