Continuous consecutive reactions with inter-reaction solvent exchange by membrane separation
File(s)
Published version
Accepted version
Author(s)
Type
Journal Article
Abstract
Pharmaceutical production typically involves multiple reaction steps with separations between successive reactions. Two processes which complicate the transition from batch to continuous operation in multistep synthesis are solvent exchange (especially high‐boiling‐ to low‐boiling‐point solvent), and catalyst separation. Demonstrated here is membrane separation as an enabling platform for undertaking these processes during continuous operation. Two consecutive reactions are performed in different solvents, with catalyst separation and inter‐reaction solvent exchange achieved by continuous flow membrane units. A Heck coupling reaction is performed in N,N‐dimethylformamide (DMF) in a continuous membrane reactor which retains the catalyst. The Heck reaction product undergoes solvent exchange in a counter‐current membrane system where DMF is continuously replaced by ethanol. After exchange the product dissolved in ethanol passes through a column packed with an iron catalyst, and undergoes reduction (>99 % yield).
Date Issued
2016-10-17
Date Acceptance
2016-09-12
Citation
Angewandte Chemie International Edition, 2016, 55 (43), pp.13576-13579
ISSN
1433-7851
Publisher
Wiley
Start Page
13576
End Page
13579
Journal / Book Title
Angewandte Chemie International Edition
Volume
55
Issue
43
Copyright Statement
© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co.
KGaA. This is an open access article under the terms of the Creative
Commons Attribution License, which permits use, distribution and
reproduction in any medium, provided the original work is properly
cited.
KGaA. This is an open access article under the terms of the Creative
Commons Attribution License, which permits use, distribution and
reproduction in any medium, provided the original work is properly
cited.
License URL
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Novartis Pharma AG
Engineering and Physical Sciences Research Council
Identifier
https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201607795
Grant Number
EP/J014974/1
5710002924
EP/J014974/1
Subjects
Science & Technology
Physical Sciences
Chemistry, Multidisciplinary
Chemistry
flow chemistry
homogeneous catalysis
membranes
solvent exchange
synthesis design
CONTINUOUS-FLOW
ORGANIC-SYNTHESIS
NANOFILTRATION
PHARMACEUTICALS
CATALYSTS
CHEMISTRY
flow chemistry
homogeneous catalysis
membranes
solvent exchange
synthesis design
03 Chemical Sciences
Organic Chemistry
Publication Status
Published
Date Publish Online
2016-09-27