A flow electrochemistry-enabled synthesis of 2-substituted N-(methyl-d)piperidines
A flow electrochemistry-enabled synthesis of 2-substituted N-(methyl-d)piperidines
A synthesis of N-monodeuteriomethyl-2-substituted piperidines is described. An efficient and readily scalable anodic methoxylation of N-formylpiperidine in an undivided microfluidic electrolysis cell delivers methoxylated piperidine 3, which is a precursor to a N-formyliminium ion and enables C-nucleophiles to be introduced at the 2-position. The isotopically labelled N-deuteriomethyl group is installed using the Eschweiler-Clarke reaction with formic acid-d2 and unlabelled formaldehyde. Monodeuterated N-methyl groups in these molecular systems possess small isotropic proton chemical shift differences important in the investigation of molecules that are able to support long-lived nuclear spin states in solution nuclear magnetic resonance.
NMR, flow electrosynthesis, long-lived nuclear spin, monodeuterated
361-368
Hadedi, Azzam A.M.
84c4d61e-3c6f-43e4-a43c-534f54a716eb
Sawyer, Stuart
43fe81b8-f66d-4299-ab7a-a91122c8e69a
Elliott, Stuart J.
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Green, Robert A
da1a32a9-4643-49fb-842c-8fb733ce553c
O’leary, Daniel J.
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Brown, Richard C.D.
21ce697a-7c3a-480e-919f-429a3d8550f5
Brown, Lynda J.
75aa95fa-5d27-46a7-9dbe-0f465a664f5b
December 2022
Hadedi, Azzam A.M.
84c4d61e-3c6f-43e4-a43c-534f54a716eb
Sawyer, Stuart
43fe81b8-f66d-4299-ab7a-a91122c8e69a
Elliott, Stuart J.
6cc724de-f75f-4c0f-a00a-e712b4e73b12
Green, Robert A
da1a32a9-4643-49fb-842c-8fb733ce553c
O’leary, Daniel J.
46a2d9e6-69c3-4f41-a29d-155af09b4dc8
Brown, Richard C.D.
21ce697a-7c3a-480e-919f-429a3d8550f5
Brown, Lynda J.
75aa95fa-5d27-46a7-9dbe-0f465a664f5b
Hadedi, Azzam A.M., Sawyer, Stuart, Elliott, Stuart J., Green, Robert A, O’leary, Daniel J., Brown, Richard C.D. and Brown, Lynda J.
(2022)
A flow electrochemistry-enabled synthesis of 2-substituted N-(methyl-d)piperidines.
Journal of Labelled Compounds and Radiopharmaceuticals, 65 (14), .
(doi:10.1002/jlcr.4006).
Abstract
A synthesis of N-monodeuteriomethyl-2-substituted piperidines is described. An efficient and readily scalable anodic methoxylation of N-formylpiperidine in an undivided microfluidic electrolysis cell delivers methoxylated piperidine 3, which is a precursor to a N-formyliminium ion and enables C-nucleophiles to be introduced at the 2-position. The isotopically labelled N-deuteriomethyl group is installed using the Eschweiler-Clarke reaction with formic acid-d2 and unlabelled formaldehyde. Monodeuterated N-methyl groups in these molecular systems possess small isotropic proton chemical shift differences important in the investigation of molecules that are able to support long-lived nuclear spin states in solution nuclear magnetic resonance.
Text
Flow Electrochem Syn N-(Methyl-d)piperidines Brown revised
- Accepted Manuscript
Text
Labelled Comp Radiopharmac - 2022 - AL‐Hadedi - A flow electrochemistry‐enabled synthesis of 2‐substituted N‐ methyl‐d (1)
- Version of Record
More information
Accepted/In Press date: 20 October 2022
e-pub ahead of print date: 22 October 2022
Published date: December 2022
Additional Information:
Funding Information:
The authors acknowledge financial support from Engineering and Physical Sciences Research Council (EP/L003325/1 and EP/P013341/1) and thank O. Maduka Ogba for insightful discussions.
Publisher Copyright:
© 2022 The Authors. Journal of Labelled Compounds and Radiopharmaceuticals published by John Wiley & Sons Ltd.
Keywords:
NMR, flow electrosynthesis, long-lived nuclear spin, monodeuterated
Identifiers
Local EPrints ID: 471753
URI: http://eprints.soton.ac.uk/id/eprint/471753
ISSN: 0362-4803
PURE UUID: ace488fe-13b3-4846-8d98-9d919daa7f57
Catalogue record
Date deposited: 17 Nov 2022 17:44
Last modified: 17 Mar 2024 02:47
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Contributors
Author:
Azzam A.M. Hadedi
Author:
Stuart Sawyer
Author:
Stuart J. Elliott
Author:
Robert A Green
Author:
Daniel J. O’leary
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