2-Ethoxy-3-fluoropyridine - ≥95% , CAS No.858675-63-5

CAS: 858675-63-5 Cat. No.: E1051201 Formula: C₇H₈FNO Peso molecolare: 141.140

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Specifiche e purezza

≥95%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥95%

Nomi e identificatori

• Sorrisi canonici: CCOC1=C(C=CC=N1)F
• IUPAC Name: 2-ethoxy-3-fluoropyridine
• InChIKey: RGMQSIXIQVIKOC-UHFFFAOYSA-N
• INCHI: 1S/C7H8FNO/c1-2-10-7-6(8)4-3-5-9-7/h3-5H,2H2,1H3
• Peso molecolare: 141.140

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic oxygen compounds
    • Classe Organooxygen compounds
      • Subclass Ethers

• Kingdom: Organic compounds
• Superclass: Organic oxygen compounds
• Classe: Organooxygen compounds
• Subclass: Ethers
• Intermediate Tree Nodes: Not available
• Direct Parent: Alkyl aryl ethers
• Alternative Parents: Pyridines and derivatives Aryl fluorides Heteroaromatic compounds Azacyclic compounds Organonitrogen compounds Organofluorides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Alkyl aryl ether - Pyridine - Aryl halide - Aryl fluoride - Heteroaromatic compound - Azacycle - Organoheterocyclic compound - Organic nitrogen compound - Hydrocarbon derivative - Organonitrogen compound - Organofluoride - Organohalogen compound - Aromatic heteromonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as alkyl aryl ethers. These are organic compounds containing the alkyl aryl ether functional group with the generic formula R-O-R' , where R is an alkyl group and R' is an aryl group.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Proprietà chimiche e fisiche

• Peso molecolare: 141.140 g/mol
• XLogP3: 1.600
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 141.059 Da
• Monoisotopic Mass: 141.059 Da
• Topological Polar Surface Area: 22.100 Ų
• Heavy Atom Count: 10
• Formal Charge: 0
• Complexity: 99.600
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

No bioanalytical assay protocols (e.g., WB, IHC, IF, FC) are applicable to this small-molecule building block. For synthetic applications, see Reaction Conditions and Synthetic Utility for general procedures (SNAr, dealkylation, N-oxidation). Reaction setup should be tailored to the chosen nucleophile and solvent system, with appropriate controls and analytical monitoring (e.g., 1H/13C/19F NMR, LC-MS).

Biological Roles

This product is intended strictly for research use. No therapeutic or clinical claims are made.

General biochemical context (literature):

• Pyridine is a common heteroaromatic motif in medicinal chemistry scaffolds due to its tunable basicity, hydrogen-bond accepting character, and capacity to modulate solubility and metabolic stability.
• Fluorination at an aryl position often alters lipophilicity, metabolic soft spots, and pKa of nearby functionalities. In heteroarenes like pyridines, a ring fluorine can also serve as a handle for SNAr-driven diversification in lead optimization programs.
• The 2-alkoxypyridine substructure can act as a weakly coordinating heteroarene, participating in metal-binding or π–π interactions in biomolecular recognition motifs (contextual to structure-based design).

Typical uses for this compound in life-science research (non-clinical):

• Intermediate for assembling probe molecules, small-molecule ligands, and heteroaryl fragments for screening decks.
• Precursor to 3-substituted-2-alkoxypyridines or 2-hydroxypyridines that feature in kinase, GPCR, or enzyme inhibitor chemotypes (literature precedent, not specific to this item).

Note: Any biological evaluation should be conducted under appropriate institutional approvals. Physicochemical properties and ADME-relevant parameters must be experimentally determined for the specific analog synthesized from this building block.

Buffer Applications

This compound is a heteroaromatic building block rather than a buffering reagent. It is not typically used to prepare biochemical buffers or pH standards. For aqueous manipulations, one may generate a pyridinium salt by protonation to aid solubility, but that is application-specific and not a standardized buffer system. See the Synthetic Utility and Reaction Conditions sections for more relevant guidance.

Green Alternatives

Because 2-ethoxy-3-fluoropyridine is a building block, greener practice centers on solvent and base choices and avoidance of problematic reagents.

Greener medium choices (general):

• Replace DMF/NMP with 2-MeTHF, CPME, or MeCN when feasible; these often support SNAr with appropriate base/catalyst and are easier to remove with better EHS profiles.
• Favor carbonate bases (K2CO3, Cs2CO3) over strong alkoxides in high-boiling polar aprotics; pair with phase-transfer agents to enhance rates.

Comparison (typical literature guidance):

• DMF/DMSO: high solubilizing power; reproductive toxicity concerns (DMF), difficult workup.
• 2-MeTHF: biomass-derived, water-immiscible (facilitates extraction), compatible with bases; may require higher temperature for complete dissolution.
• MeCN: low viscosity, low boiling; toxicity manageable; wide SNAr precedent.
• Green alcohols (EtOH, i-PrOH): feasible for salt formation and some substitutions; may compete as nucleophiles.

Small decision table (general):

• Goal: SNAr amination → Try MeCN or 2-MeTHF + Cs2CO3, 60–90 °C; fallback to DMF for difficult substrates.
• Goal: Thiolation → 2-MeTHF or toluene with in situ NaSAr or K2CO3/MeCN; avoid DMF if odor control is critical.
• Goal: Hydrolysis/dealkylation → AcOH/H2O systems or organic acids (TFA) vs halogenated acids.

Waste minimization:

• Use catalytic phase transfer or microwave heating to shorten times.
• Apply telescoped sequences (e.g., SNAr → quench → direct crystallization of pyridinium salts) to reduce solvent exchanges.

Pharmaceutical Uses

No excipient or pharmacopeial role is specified for this item; refer to CoA/Spec Sheet for any compliance details if applicable. In pharmaceutical R&D, 2-ethoxy-3-fluoropyridine is best viewed as a synthetic intermediate.

Formulation/manufacturing context (general, non-therapeutic):

• Serves as a heteroaryl building block in API route scouting, enabling rapid installation of 3-substituents by SNAr prior to late-stage functional group adjustments.
• The pyridine nitrogen allows salt formation for purification/crystallization during process development.
• Fluorine at C-3 can be a strategic leaving group for convergent couplings with nucleophilic partners, reducing reliance on metal-catalyzed aryl fluoride activation.

Quality considerations for GMP development (general):

• Control for regioisomer content and residual halides/solvents; verify with orthogonal analytics (NMR/LC/GC/HRMS).
• Define impurity fate-and-purge if incorporated into a multistep API synthesis.

Regulatory note:

• For research use only. Not intended for human or veterinary use, drug substance, drug product, or diagnostic applications without further qualification and regulatory assessment.

Physical Properties

Item-specific specifications (for this catalog entry):

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.

Literature/computed (informational; not item specifications):

• Molecular formula: C7H8FNO (computed)
• Molecular weight: 141.14 g/mol (computed)
• Acid–base: basic heteroaromatic nitrogen (conjugate-acid pKa typically ~5–6 for pyridinium derived from substituted pyridines; literature ranges)
• Polarity: polar, aprotic heteroaryl compound; capable of hydrogen-bond acceptance (ring N, ether O) but not donation.
• Volatility: low-to-moderate (typical for small substituted pyridines; specific BP not listed here—consult literature or CoA).
• Solubility (qualitative, literature): miscible with common organic solvents (e.g., ethers, esters, chlorinated solvents); moderate water solubility expected for pyridine derivatives but strongly dependent on pH (protonated form is water-soluble).
• LogP/logD: substituted pyridines with one ether and one fluorine typically show modest lipophilicity; exact value not provided—consult predictive tools or literature for method development.
• Refractive index, density, UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.

Practical notes (general):

• The pyridine nitrogen can be protonated to improve aqueous solubility for workups.
• The aryl C–F and ether substituent can influence GC detectability and retention; LC–UV at 254 nm typically gives a response for pyridine aromatics (literature).

Quality and Grades

• Grade/Purity for this item: Not specified for this item; refer to CoA/Spec Sheet.

How to interpret grades (general guidance):

• Analytical Reagent (AR)/ACS grade typically ensures low levels of common inorganic/organic impurities and suitability for general analytical and synthetic work.
• HPLC grade emphasizes very low UV-absorbing impurities and particulate content for chromatographic applications.
• Synthesis grade focuses on consistent performance in reactions; may not control UV background to HPLC-grade levels.

Impurity considerations for this structure (general):

• Potential regioisomeric impurities (e.g., alternative substitution patterns on the pyridine ring) may be present if synthesis involves electrophilic or nucleophilic substitution on a substituted pyridine scaffold.
• Residual halogenated or alkoxy precursors and inorganic salts may persist from SNAr or alkylation steps; appropriate workup and drying are typical.
• Moisture and basicity: the pyridine nitrogen can sequester trace acids; residual acid/base may influence NMR chemical shifts and chromatographic behavior.

Documentation and verification:

• For regulated work, verify identity by orthogonal methods: 1H/13C NMR (diagnostic ethoxy quartet/triplet, aromatic pattern), 19F NMR (single aryl F signal), HRMS (M+), and chromatographic purity (GC/LC).
• Item-specific limits (water content, residual solvents, metals, UV cutoff, stabilizers) are Not specified for this item; refer to CoA/Spec Sheet.

Reaction and Applications

As a functionalized fluoropyridine, 2-ethoxy-3-fluoropyridine is a versatile synthon for heteroaryl elaboration.

Key reaction families (literature/general):

• Nucleophilic aromatic substitution (SNAr) at C-3: Aryl–F on an electron-deficient pyridine ring is activated to displacement by N-, O-, S-, and C-nucleophiles. Amination (to anilides/anilines), thiolation (to aryl thioethers), and alkoxylation are common under basic conditions.
• Ether manipulation at C-2: Acidic conditions (e.g., HBr/AcOH, TFA, strong mineral acids) can cleave the ethoxy substituent to furnish the corresponding 2-hydroxypyridine or facilitate O-to-N rearrangements in related systems (literature). Mitsunobu or silyl-assisted strategies may be used when selective dealkylation is required.
• Ring nitrogen chemistry: Salt formation, N-oxide formation (mCPBA, peracids) to enable Polonovski/Meerwein-like rearrangements or regioselective substitutions at other ring positions.
• Directed metalation: The 2-alkoxy group can modulate acidity at adjacent positions; with strong bases (e.g., LDA, s-BuLi/TMEDA) at low temperature, selective deprotonation at designated ring carbons may be achieved for further functionalization (requires optimization).

Applications in synthesis (general):

• Late-stage installation of heteroaryl motifs in agrochemical and materials leads.
• Library synthesis: rapid diversification via SNAr with amines/thiols provides SAR arrays of 3-substituted 2-alkoxypyridines.
• Intermediate toward 2-hydroxypyridinyl scaffolds after ethoxy removal.

Practical tips:

• Ensure rigorous base selection for SNAr (Cs2CO3 > K2CO3 for sluggish aminations). Add phase-transfer catalysts for heterogeneous systems. Control moisture for alkoxide/thiolate generation.

Reaction Conditions

General literature guidance for typical transformations of 2-ethoxy-3-fluoropyridine (not item specifications):

• SNAr amination at C-3:

  • Solvent: MeCN, 2-MeTHF, or DMF/DMSO for difficult cases.
  • Base: K2CO3 or Cs2CO3 (2–3 equiv); for anilines, Cs2CO3 often superior; for aliphatic amines, K2CO3 suffices.
  • Temperature: 60–110 °C depending on nucleophile strength; 2–16 h.
  • Notes: Add catalytic KI or phase-transfer agents for heterogeneous systems. Monitor by 19F NMR or LC-MS. Typical isolated yields for activated Ar–F SNAr: 60–90% (literature).

• SNAr thiolation/alkoxylation:

  • Generate thiolate/alkoxide in situ with NaH or K2CO3 in MeCN/2-MeTHF; 25–80 °C, 1–8 h.
  • For sensitive thiols, use mild bases (K2CO3) and crown ether to enhance rate.

• Acidic dealkylation (2-ethoxy → 2-hydroxy):

  • Reagents: HBr/AcOH, conc. H2SO4, or TFA; solvent can be AcOH or neat acid.
  • Conditions: Reflux to 120 °C depending on acid strength; 1–6 h.
  • Workup: Neutralize, extract, and, if desired, isolate as pyridinium salt for ease of handling.

• N-oxidation:

  • Reagent: mCPBA (1.1–1.5 equiv) in CH2Cl2 or MeCN, 0–25 °C, 1–3 h; enables downstream regioselective substitutions.

Always perform small-scale scouting and adjust equivalents/temperature to the specific nucleophile and substitution pattern. Employ dry glassware and inert atmosphere for moisture-sensitive bases.

Safety and Handling

Authoritative safety information must be taken from the product SDS.

Item-specific hazard information (from Product Data):

• Signal Word: Not specified for this item; refer to SDS.
• H-Statements: Not specified for this item; refer to SDS.
• GHS Classification/Pictograms: Not specified for this item; refer to SDS.

General safety guidance for substituted pyridines and aryl fluorides (informational):

• Likely hazards: may cause skin/eye irritation and respiratory tract irritation; many low-MW pyridines are combustible liquids and have strong odors. Treat as harmful if swallowed or inhaled (literature/general).
• PPE: use lab coat, nitrile gloves, and splash goggles; handle in a fume hood to minimize inhalation exposure.
• Storage incompatibilities: avoid strong oxidizers and strong acids/bases unless intended for reaction; strong acids will protonate the pyridine nitrogen and can cleave the ethoxy group under forcing conditions (hydrolysis).
• Handling: minimize exposure to air and moisture during moisture-sensitive transformations; keep containers tightly closed. Use inert atmosphere for air/moisture-sensitive reactions.
• First-aid overview (general): move to fresh air if inhaled; flush with water for 15 minutes if in eyes/skin; remove contaminated clothing; seek medical attention as needed. Spill cleanup with inert absorbent; dispose per local regulations.
• Fire safety: use CO2, dry chemical, or foam; cool containers with water spray. Combustion may produce NOx, HF, and CO/CO2; firefighters should wear SCBA (general guidance).

Always consult the Aladdin Scientific SDS for this specific SKU before use.

Solvent Selection

Compound role: 2-Ethoxy-3-fluoropyridine is typically a heteroaromatic building block rather than a bulk solvent. Solvent selection is therefore about dissolving it and enabling its key transformations (e.g., SNAr at C-3, acid- or base-mediated reactions, salt formation).

Solubility/miscibility profile (general/literature):

• High solubility in polar aprotic media: DMF, DMSO, NMP, DMAc; good in MeCN, THF, 2-MeTHF, EtOAc, and CH2Cl2. Variable in alcohols and alkanes; increased aqueous solubility upon protonation with mineral or organic acids (e.g., HCl, TsOH).

Choosing a medium by transformation:

• SNAr with amines/thiols/alkoxides: DMF/DMSO/NMP or 2-MeTHF/MeCN for greener options; include base (K2CO3, Cs2CO3, NaH, or organic superbases as appropriate).
• Acidic hydrolysis/dealkylation at C-2 O-alkyl: use protic acidic solvents (AcOH, TFA, HBr/AcOH mixtures) or biphasic acid systems.
• Metalation or N-oxide chemistry: THF/2-MeTHF or toluene/THF mixtures under inert atmosphere.

Quick comparison (general):

• DMF/DMSO: maximal activation/solubility; higher EHS burden and challenging removal.
• 2-MeTHF/CPME: greener, facilitate extractions, compatible with bases; may require heating for full solubility.
• MeCN: good balance of polarity/volatility; may need stronger bases for sluggish SNAr.

Tip: If salt formation is desired for isolation or crystallization, switch to alcohol/ether mixtures and add acid to precipitate the pyridinium salt.

Storage and Reconstitution

• Storage Conditions (Product Data): Room temperature.
• Shipped In: Not specified for this item; refer to CoA/Spec Sheet.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Reconstitution: Not typically applicable; this is a neat organic building block. If received as a solidified mass or for solution preparation, dissolve in an appropriate dry organic solvent (e.g., MeCN, THF, EtOAc) under ambient conditions.

Good practice (general):

• Keep container tightly closed in a dry, well-ventilated place. Protect from strong acids/bases unless intended for reaction.
• For prolonged storage, consider maintaining under inert gas to minimize oxidative discoloration or moisture uptake.
• If forming salts for handling (e.g., HCl salt), store according to the salt’s stability profile and avoid repeated exposure to atmospheric moisture.

Research Use Note: For research use only.

Structure and Identity

Brief description: 2-Ethoxy-3-fluoropyridine is a monosubstituted fluoropyridine bearing an ethoxy substituent ortho to the ring nitrogen and a fluorine at the 3-position, providing an electron-deficient heteroaromatic scaffold useful for nucleophilic substitution and diversification.

• SKU: E1051201
• Product Name: 2-Ethoxy-3-fluoropyridine
• CAS: 858675-63-5 (Product Data)
• PubChem CID: 70700959 (Product Data)
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet. (Product Data lists: "315789", which is non-standard; defer to CoA)
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Formula: C7H8FNO (computed/literature)
• Molecular Weight: 141.14 g/mol (computed from formula; literature)

Structural features (general description):

• Heteroaromatic six-membered ring containing one ring nitrogen (pyridine core).
• Substituents: –OCH2CH3 at C-2 (adjacent to ring N) and –F at C-3.
• Functional groups: aromatic C–F (activated toward SNAr on a pyridine ring), aryl ether (2-ethoxypyridine motif), tertiary ring nitrogen (basic site capable of salt formation and coordination).
• 2D topology in words: a pyridine ring in which the ring nitrogen is position 1; an ethoxy group is attached at position 2; a fluorine atom at position 3; positions 4–6 are unsubstituted carbons.

Note: Identity fields not explicitly provided in the Product Data (e.g., exact SMILES/InChIKey) should be confirmed from the item’s CoA/Spec Sheet prior to regulated or scale-up work.

Synthetic Utility

Functional handles and reactivity (literature/general):

• Activated aryl C–F at C-3 enables efficient SNAr with a wide range of nucleophiles (amines, thiols, alkoxides, stabilized carbanions). The adjacent ring N enhances activation.
• The 2-ethoxy substituent offers orthogonal chemistry: controlled dealkylation to the 2-hydroxy, or preservation as an electron-donating group to tune ring electronics.
• The pyridine nitrogen supports salt formation, N-oxide chemistry, and metal coordination (useful for directing group strategies or transient activation).

Retrosynthetic value:

• Serves as a masked 2-hydroxypyridine synthon: late-stage acidolysis swaps ethoxy for hydroxy.
• Acts as a hub for parallel synthesis via SNAr diversification at C-3, followed by further functionalization at C-4/5/6 through directed metalation or electrophilic substitution (after appropriate activation).

Named/typical transformations:

• SNAr amination (Buchwald–Hartwig alternatives not required due to activated Ar–F).
• Thiolation/alkoxylation under basic conditions.
• N-oxidation (mCPBA) → regioselective substitution patterns via the N-oxide route.
• Dealkylation/hydrolysis under acidic media to 2-hydroxypyridine.

Practical synthesis tips:

• Use polar aprotic solvents or greener substitutes; select base strength to match nucleophile pKa.
• Monitor by 19F NMR for rapid assessment of Ar–F consumption.
• Quench to pyridinium salts when crystallization assists purification; back-neutralize for free base recovery.

Target Specificity

Not applicable. This product is a small-molecule building block and is not an antibody, enzyme, or affinity reagent. No target, epitope, or biological specificity is defined for this SKU. See Reaction & Applications and Synthetic Utility for relevant use cases.