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A flow electrochemistry‐enabled synthesis of 2‐substituted N ‐(methyl‐ d )piperidines
Author(s) -
ALHadedi Azzam A. M.,
Sawyer Stuart,
Elliott Stuart J.,
Green Robert A.,
O'Leary Daniel J.,
Brown Richard C. D.,
Brown Lynda J.
Publication year - 2022
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.4006
Subject(s) - chemistry , piperidine , electrochemistry , formic acid , nucleophile , molecule , formaldehyde , electrolysis , stereochemistry , organic chemistry , electrode , electrolyte , catalysis
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‐ d 2 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.