Cefonicid is a common second-generation cephalosporin, and the 7-amino-3-[sulphomethyl-1- H -tetrazol-5-yl-thiomethyl]-3-cephem-4-carboxylate monosodium salt is a key synthetic intermediate in its preparation. Despite the considerable international demand for this antibiotic, its preparation is hampered by low synthetic yield, long reaction time, and time-consuming industrial filtration over charcoal after the purification step. In the context of the industrial production of pharmaceutical intermediates, in which the balance between streamlining and enhancing productivity is necessary in order to compete in the global active pharmaceutical ingredients (API) market, we have investigated an efficient and practical procedure for the synthesis of a key cefonicid intermediate that features a telescopic route whose synthetic steps are all performed at room temperature; from the displacement of the acetoxy group with boron trifluoride to crystallization without treatment with charcoal. In other words, a simpler, scalable, cost-effective and energy-saving protocol is herein reported as a means of moving towards commercial manufacturing. The optimization of the process parameters and the industrial-scale impact assessment should pave the way for industrialization.

中文翻译：

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室温下关键头孢尼西中间体的高效中试合成

头孢尼西是常见的二代头孢菌素，其制备过程中的关键合成中间体是7-氨基-3-[磺甲基-1-H-四唑-5-基-硫甲基]-3-头孢烯-4-羧酸单钠盐. 尽管国际上对这种抗生素有相当大的需求，但其制备受到合成产率低、反应时间长以及纯化步骤后用木炭进行耗时的工业过滤的阻碍。在医药中间体的工业生产背景下，为了在全球活性药物成分 (API) 市场竞争，精简和提高生产力之间的平衡是必要的，我们研究了一种有效且实用的合成关键头孢尼西中间体的方法，该中间体具有伸缩路线，其合成步骤均在室温下进行；从用三氟化硼取代乙酰氧基到不用木炭处理结晶。换言之，本文报告了一种更简单、可扩展、具有成本效益和节能的协议，作为转向商业制造的一种手段。工艺参数的优化和工业规模的影响评估应该为工业化铺平道路。本文报告了具有成本效益和节能的协议作为转向商业制造的一种手段。工艺参数的优化和工业规模的影响评估应该为工业化铺平道路。本文报告了具有成本效益和节能的协议作为转向商业制造的一种手段。工艺参数的优化和工业规模的影响评估应该为工业化铺平道路。