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.
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.
Qian
Zizheng
Z
Innovative Technology Centre, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW UK.
Baxendale
Ian R
IR
Ley
Steven V
SV
D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010880:Piperidines; D017465:Receptors, Opioid, delta / Q000819:agonists*; D013055:Spectrophotometry, Infrared
D001549:Benzamides; C555319:N,N-diethyl-4-(3-fluorophenylpiperidin-4-ylidenemethyl)benzamide; D010879:Piperazines; D010880:Piperidines; D017465:Receptors, Opioid, delta