Quality-In(Process)Line (QuIProLi) process intensification for a micro-flow UV-photo synthesis enabled by online UHPLC analysis

TETRAHEDRON

卷:74

Article

Escriba-Gelonch, Marc¹  Shahbazali, Elnaz¹  Honing, Maarten²  Hessel, Volker¹ 

[1] Eindhoven Univ Technol, Dept Chem Engn & Chem, Grp Micro Flow Chem & Proc Technol, Rondom 70, NL-5612 AP Eindhoven, Netherlands

[2] Maastricht Univ, Imaging Mass Spectrometry, Minderbroedersberg 4-6, NL-6211 LK Maastricht, Netherlands

关键词: Process automation;    Flow chemistry;    Fast-sampling;    UHPLC;    Photo-Claisen rearrangement;   

DOI  :  10.1016/j.tet.2018.02.016

来源: Elsevier

【 摘 要 】

Process intensification commonly enables reaction acceleration and therefore continuous-flow/PAT is urgently needed. The low volumes typical for micro-flow pose challenges for online sampling operations in analytics. In this paper, a very fast process is combined with a modified ultra-high-performance liquid chromatography (UHPLC) system allowing for very fast sampling and analysis. Low-volume online sampling according to the needs posed by PAT for pharma quality control, is introduced here for UHPLC analysis of the photo-Claisen rearrangement in micro-flow. Chances and challenges are critically reviewed, including the reproducibility and robustness of the sampling. Furthermore, the ability and speed of the chosen set-up in order to capture process changes and adjust the process parameters properly is investigated. With the applied online sampling system, it was possible to perform, almost unattended and spending 12 times less sampling volume, a full factorial analysis of all relevant reaction conditions (243 experiments) in three days. Such quality-in-the-process-line (QuIProLi) online sampling avoided random errors due to automation. (C) 2018 Elsevier Ltd. All rights reserved.

【 授权许可】

Free