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A Continuous Flow Process Using a Sequence of Microreactors with In‐line IR Analysis for the Preparation of N,N‐Diethyl‐4‐(3‐fluorophenylpiperidin‐4‐ylidenemethyl)benzamide as a Potent and Highly Selective δ‐Opioid Receptor Agonist
Authors:Zizheng Qian  Dr. Ian R. Baxendale  Prof. Steven V. Ley
Affiliation:Innovative Technology Centre, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW (UK), Fax: (+44)?1223‐336442
Abstract:
This article describes the design, optimisation and development of a continuous flow synthesis of N,N‐diethyl‐4‐(3‐fluorophenylpiperidin‐4‐ylidenemethyl)benzamide, a potent δ‐opioid receptor agonist developed by AstraZeneca. The process employs a sequence of flow‐based microreactors, with integrated purification employing solid‐supported reagents and in‐line IR analytical protocols using a newly developed ReactIR flow cell. With this monitoring device, initiation of the fourth input flow stream can be precisely controlled during the synthesis.
Keywords:flow chemistry  IR spectroscopy  microreactors  solid‐phase synthesis
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