(+-)-cis-3-methyl Norfentanyl
[CAS# 33794-42-2]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Piperidines
• Name: (+-)-cis-3-methyl Norfentanyl
• Synonyms: N-[(3R,4S)-3-methylpiperidin-4-yl]-N-phenylpropanamide
• Molecular Formula: C₁₅H₂₂N₂O
• Molecular Weight: 246.35
• CAS Registry Number: 33794-42-2
• SMILES: CCC(=O)N([C@H]1CCNC[C@H]1C)C2=CC=CC=C2

Properties

• Density: 1.0±0.1 g/cm³ Calc.^*
• Boiling point: 367.0±35.0 °C 760 mmHg (Calc.)^*
• Flash point: 175.8±25.9 °C (Calc.)^*
• Index of refraction: 1.542 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P280-P305+P351+P338

Discovery and Applications

(±)-cis-3-Methyl norfentanyl is a synthetic compound structurally related to norfentanyl, which itself is the primary metabolite of fentanyl, a potent μ-opioid receptor agonist. As a modified analog, (±)-cis-3-methyl norfentanyl incorporates a methyl substitution at the 3-position of the piperidine ring and maintains the basic phenylpiperidine scaffold characteristic of fentanyl-derived substances. The designation (±)-cis refers to the presence of a racemic mixture of the two enantiomers in the cis configuration around the piperidine ring.

The discovery and synthesis of (±)-cis-3-methyl norfentanyl are linked to efforts to expand analytical capabilities in forensic and clinical toxicology for the identification of emerging synthetic opioids and their metabolites. Structurally, the compound represents a metabolite or degradation product of synthetic fentanyl analogs that have been modified at the piperidine ring to investigate structure-activity relationships or to create new fentanyl analogs with altered pharmacological profiles. The addition of a methyl group in the cis configuration can influence the molecule’s binding affinity, metabolic stability, and receptor selectivity.

Analytical characterization of (±)-cis-3-methyl norfentanyl is typically performed using high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) spectroscopy. These techniques help confirm the compound’s structure, purity, and stereochemistry. It is also evaluated using chromatographic methods such as liquid chromatography (LC) or gas chromatography (GC) combined with mass spectrometry (MS) for detection in biological matrices. The availability of such reference materials is essential for the development of sensitive and specific assays used to detect fentanyl analogs and their metabolites in toxicological investigations.

The presence of (±)-cis-3-methyl norfentanyl in forensic samples may indicate prior use or exposure to a fentanyl analog bearing a 3-methyl substituent, or it may result from intentional synthesis for research or chemical profiling purposes. Due to its close structural similarity to norfentanyl, the compound is expected to be inactive at μ-opioid receptors, as norfentanyl itself lacks the N-phenylpropionamide moiety critical for opioid activity. Nonetheless, the identification of such metabolites is crucial for understanding the biotransformation pathways of synthetic opioids and for distinguishing between different fentanyl derivatives in forensic casework.

The synthesis of (±)-cis-3-methyl norfentanyl typically involves derivatization of a 4-anilinopiperidine intermediate followed by methylation at the desired position and controlled reduction or functional group transformation to produce the cis-configured product. Stereochemical control is necessary to isolate or characterize the cis isomer, as different configurations may result in significantly altered pharmacokinetic or binding properties.

While the compound has no therapeutic application of its own, it is significant for its role as a chemical marker in the metabolism of synthetic opioids. It is commonly used as a standard in research and analytical laboratories for the identification and quantification of fentanyl analog-related substances. With the proliferation of novel synthetic opioids and the continual emergence of designer drugs, compounds such as (±)-cis-3-methyl norfentanyl are essential tools for monitoring public health and law enforcement challenges associated with opioid misuse.

References

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