从批量到NB,NZ受保护的美罗的半连续流化
Marziale Comito1,2, Riccardo Monguzzi2, Silvia Tagliapietra1
1Dipartimento di Scienza e Tecnologia del Farmaco, University of Turin, Via Pietro Giuria 9, 10125 Turin, Italy.
Pharmaceutics
|May 27, 2023
概括
微波辅助流化学为美罗合成提供了更安全,更快的方法. 这种新的协议显著减少了反应时间,同时保持了工业应用的高产品质量.
科学领域:
- 过程化学 过程化学
- 有机合成 有机合成
- 化学工程是化学工程的重要组成部分.
背景情况:
- 梅罗胺是一种关键的卡巴胺抗生素,依赖于具有挑战性的最后合成步骤,涉及异质的催化化.
- 目前的批量处理采用三相系统,由于同时去除p-nitrobenzyl (pNB) 和p-nitrobenzyloxycarbonyl (pNZ) 保护组,因此难以满足质量标准并确保安全.
研究的目的:
- 调查微波 (MW) 辅助流化学作为一种新的,工业上可行的技术,用于美罗胺解.
- 为半连续流程过程优化反应参数,旨在提高与传统批量方法相比的效率和安全性.
主要方法:
- 在温和条件下使用MW辅助流量化学探索美罗烯水解.
- 系统地调查和优化关键反应参数:催化剂负荷,温度,压力,停留时间和流量.
- 从批量过渡到半连续流程过程,评估参数对反应动力学的影响.
主要成果:
- 开发了一种新型的半连续流程协议,将居住时间优化为840秒,并利用4个周期.
- 与批量生产相比,新方法成功地将总反应时间减半 (14分钟与30分钟相比).
- 产品质量保持不变,产量略有下降 (流量70%对批量74%),但被提高的生产率所抵消.
结论:
- 兆瓦辅助流化学为工业合成梅罗胺提供了一个有前途的替代方案,提高了工艺效率和安全性.
- 开发的半连续流程协议可显著减少反应时间和提高生产率,使其具有扩展的吸引力.
- 这项技术解决了传统批量化步骤固有的挑战,为更绿色,更高效的制药制造铺平了道路.
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