Aqueous Instability of δ-Fluorobutylpiperidines
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | ChemMedChem |
Volume | 12 |
Issue number | 6 |
Pages (from-to) | 431-437 |
Number of pages | 7 |
ISSN | 1860-7179 |
DOIs | |
Publication status | Published - 17 Mar 2017 |
- Drug Stability, Fluorine/chemistry, Kinetics, Magnetic Resonance Spectroscopy, Piperidines/chemistry, Spectrometry, Mass, Electrospray Ionization, Water/chemistry
Research areas
ID: 195958758