Open AccessOlefin Metathesis in Continuous Flow Reactor Employing Polar Ruthenium Catalyst and Soluble Metal Scavenger for Instant Purification of Products of Pharmaceutical Interest
Author(s) -
Ren Wei Toh,
Michał Patrzałek,
Tomasz Nienałtowski,
Jakub Piątkowski,
Anna Kajetanowicz,
Jie Wu,
Karol Grela
Publication year - 2021
Publication title -
acs sustainable chemistry and engineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.878
H-Index - 109
ISSN - 2168-0485
DOI - 10.1021/acssuschemeng.1c06522
Subject(s) - flow chemistry , process engineering , continuous reactor , catalysis , ruthenium , chemistry , chemical engineering , combinatorial chemistry , materials science , organic chemistry , engineering
In recent years, the development of continuous-flow reactors has attracted growing attention from the synthetic community. Moreover, findings in the precise control of the reaction parameters and improved mass/heat transfer have made the flow setup an attractive alternative to batch reactors, both in academia and industry, enabling safe and easy scaling-up of synthetic processes. Even though a majority of the pharmaceutical industry currently rely on batch reactors or semibatch reactors, many are integrating flow technology because of easier maintenance and lower risks. Herein, we demonstrate an operationally simple flow setup for homogeneous ring-closing metathesis, which is applicable to the synthesis of active pharmaceutical ingredients precursors or analogues with high efficiency, low residence time, and in a green solvent. Furthermore, through the addition of a soluble metal scavenger in the subsequent step within the flow system, the level of ruthenium contamination in the final product can be greatly reduced (to less than 5 ppm). To ensure that this method is applicable for industrial usage, an upscale process including a 24 h continuous-flow reaction for more than 60 g of a Sildenafil analogue was achieved in a continuous-flow fashion by adjusting the tubing size and flow rate accordingly.