(2R,7aS)-2-fluorotetrahydro-1H-Pyrrolizine-7a(5H)-methanol
[CAS 2097518-76-6]

Identification

• Classification: Organic raw materials >> Alcohols, phenols, phenolic compounds and derivatives
• Name: (2R,7aS)-2-fluorotetrahydro-1H-Pyrrolizine-7a(5H)-methanol
• Synonyms: [(2R,8S)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolizin-8-yl]methanol
• Molecular Formula: C₈H₁₄FNO
• Molecular Weight: 159.20
• CAS Registry Number: 2097518-76-6
• EC Number: 882-537-8
• SMILES: C1C[C@]2(C[C@H](CN2C1)F)CO

Properties

• Solubility: Very Soluble (205 g/L) (25 °C), Calc.^*
• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 225.6±15.0 °C 760 mmHg (Calc.)^*
• Flash point: 90.2±20.4 °C (Calc.)^*
• Index of refraction: 1.517 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2021 ACD/Labs)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

chemBlink Chemical Story

Why would medicinal chemists care about a small bicyclic amino alcohol with a fluorine atom? CAS 2097518-76-6, ((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)methanol, has become notable because this compact chiral framework appears in the chemistry of inhibitors directed at KRAS G12D, one of the most important oncogenic mutations.

KRAS is a molecular switch that cycles between GDP- and GTP-bound states and helps control cell-growth signaling. Mutations can lock the pathway into abnormal signaling. For many years KRAS was regarded as exceptionally difficult to drug because its surface offered few obvious small-molecule pockets and because the protein binds guanine nucleotides very tightly. The success of covalent KRAS G12C inhibitors changed that perception, but G12D presents a different chemical problem: aspartate replaces glycine at position 12, so the reactive cysteine exploited by G12C drugs is absent.

Recent KRAS G12D programs therefore rely on different binding strategies and carefully shaped three-dimensional molecules. This is where the fluorinated pyrrolizine alcohol becomes interesting. Its fused bicyclic amine constrains the molecule into a defined shape rather than allowing a flexible chain to explore many conformations. The stereochemistry fixes the spatial relationship between the nitrogen, fluorinated carbon, and hydroxymethyl group. Medicinal chemists can then use the alcohol as a point for further attachment while the bicyclic core occupies a precisely defined region of a larger inhibitor.

The fluorine atom is also purposeful. Carbon-fluorine substitution can influence local conformation, polarity, basicity of nearby amines, metabolic stability, and protein binding. In a rigid chiral scaffold, even a single fluorine may change how the entire fragment presents itself to a target. The result is a small building block carrying unusually dense three-dimensional information.

Its synthesis is correspondingly demanding. Published patent work on scalable preparation emphasizes stereochemical control and construction of the fused pyrrolizine core, reflecting a common challenge in modern medicinal chemistry: once a three-dimensional fragment proves valuable, the discovery route must be converted into a practical manufacturing route with high enantiomeric purity.

This compound therefore tells a broader story about drug design after the era of flat aromatic fragments. Modern oncology increasingly depends on rigid, stereodefined building blocks that position functional groups with molecular precision. CAS 2097518-76-6 is memorable not because it is an inhibitor by itself, but because its "butterfly-shaped" chiral scaffold helps chemists build molecules aimed at a mutation that was once considered extremely difficult to target.

References:
1. PubChem, ((2R,7aS)-2-Fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)methanol, CID 118109097.
2. WO2024092420A1, Preparation method for ((2R,7aS)-2-fluorohexahydro-1H-pyrrolizin-7a-yl)methanol.
3. MedChemExpress, CAS 2097518-76-6, KRAS G12D inhibitor building block.

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