Abstract
In a series of partially fluorinated N-propyl- and N-butylpiperidine derivatives, three compounds were found to exhibit unexpected instability under mild biophysical assay conditions. These compounds carry a single terminal fluorine in the δ-position of an N-butyl group as a common structural feature. An adjacent fluorine substituent at the γ-position significantly slows down the reactivity. All other compounds, having either no or more than one fluorine substituent at the δ-position are chemically inert under all assay conditions. The reactivity of the labile compounds is traced to an intramolecular ring-closing fluorine substitution reaction by the moderately basic piperidine unit, leading to a spiro-pyrrolidinium salt. The chemical lability of δ-monofluorinated or γ,δ-difluorinated N-butylpiperidine derivatives even under very mild biophysical assay conditions constitutes a caveat to the molecular design of partially fluorinated alkylamines.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | ChemMedChem |
| Vol/bind | 12 |
| Udgave nummer | 6 |
| Sider (fra-til) | 431-437 |
| Antal sider | 7 |
| ISSN | 1860-7179 |
| DOI | |
| Status | Udgivet - 17 mar. 2017 |