The development of a scalable telescoped continuous flow procedure for difluoromethylation of a protected amino acid with fluoroform (CHF₃, R-23) gas and subsequent high temperature deprotection to provide eflornithine, an important Active Pharmaceutical Ingredient (API), is described. Eflornithine is used for the treatment of sleeping sickness and hirsutism, and it is on the World Health Organization’s list of essential medicines. Fluoroform is produced in large quantities as a side product in the manufacture of polytetrafluoroethylene (PTFE, Teflon). Fluoroform is an ozone-benign and nontoxic gas, but its release into the environment is forbidden under the Kyoto protocol owing to its high global warming potential. The existing manufacturing route to eflornithine uses chlorodifluoromethane (CHClF₂, R-22) which will be phased out under the Montreal protocol; therefore, the use of the fluoroform presents a viable cost-effective and more sustainable alternative. The process parameters and equipment setup were optimized on laboratory scale for the two reaction steps to improve product yield and scalability. The telescoped flow process utilizing fluoroform gas was operated for 4 h to afford the target molecule in 86% isolated yield over two steps with a throughput of 24 mmol/h.

中文翻译：

---

氟仿为二氟甲基源的可扩展连续流法合成紫花碱

描述了可伸缩的连续式连续流程序的开发，该程序用于用氟仿（CHF ₃，R-23）气体对受保护的氨基酸进行二氟甲基化，然后进行高温脱保护以提供一种重要的活性药物成分（API）依氟鸟氨酸。依氟鸟氨酸用于治疗昏睡病和多毛症，并且在世界卫生组织的基本药物目录中。氟仿是生产聚四氟乙烯（PTFE，聚四氟乙烯）时的副产品，被大量生产。氟仿是一种有益于臭氧的无毒气体，但由于其较高的全球变暖潜能，《京都议定书》禁止将其释放到环境中。现有的向氟氯乙胺的生产路线使用氯二氟甲烷（CHClF₂，R-22），将根据《蒙特利尔议定书》逐步淘汰；因此，使用氟仿是一种可行的成本有效且更具可持续性的替代方法。在实验室规模上针对两个反应步骤优化了工艺参数和设备设置，以提高产品收率和可扩展性。使用氟仿气的伸缩式流动过程进行4小时，以分两步提供目标分子的分离产率为86％，吞吐量为24 mmol / h。