Ethyl 3-fluoro-2-methoxybenzoate - ≥97% , CAS No.1106304-72-6

CAS: 1106304-72-6 Cat. No.: E948488 Summenformel: C₁₀H₁₁FO₃ Molekulargewicht: 198.190

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

Spezifikationen & Reinheit

≥97%

Storage

Room temperature

Reinheit

≥97%

Namen und Kennungen

• Kanonisches Lächeln: CCOC(=O)C1=C(C(=CC=C1)F)OC
• IUPAC Name: ethyl 3-fluoro-2-methoxybenzoate
• InChIKey: QSWABSZUZCPYEL-UHFFFAOYSA-N
• INCHI: 1S/C10H11FO3/c1-3-14-10(12)7-5-4-6-8(11)9(7)13-2/h4-6H,3H2,1-2H3
• Molekulargewicht: 198.190

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Klasse Benzene and substituted derivatives
      • Subclass Benzoic acids and derivatives
        • Ebene5 Methoxybenzoic acids and derivatives
          • Ebene6 O-methoxybenzoic acids and derivatives

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Klasse: Benzene and substituted derivatives
• Subclass: Benzoic acids and derivatives
• Intermediate Tree Nodes: Methoxybenzoic acids and derivatives
• Direct Parent: O-methoxybenzoic acids and derivatives
• Alternative Parents: Benzoic acid esters 3-halobenzoic acids and derivatives Phenoxy compounds Methoxybenzenes Benzoyl derivatives Anisoles Fluorobenzenes Alkyl aryl ethers Aryl fluorides Carboxylic acid esters Organofluorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: O-methoxybenzoic acid or derivatives - Benzoate ester - 3-halobenzoic acid or derivatives - Halobenzoic acid or derivatives - Methoxybenzene - Benzoyl - Anisole - Phenol ether - Phenoxy compound - Alkyl aryl ether - Fluorobenzene - Halobenzene - Aryl halide - Aryl fluoride - Carboxylic acid ester - Ether - Carboxylic acid derivative - Hydrocarbon derivative - Organic oxide - Organic oxygen compound - Organooxygen compound - Organohalogen compound - Organofluoride - Aromatic homomonocyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as o-methoxybenzoic acids and derivatives. These are benzoic acids in which the hydrogen atom at position 2 of the benzene ring is replaced by a methoxy 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

Chemische und physikalische Eigenschaften

• Molekulargewicht: 198.190 g/mol
• XLogP3: 2.200
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 4
• Exact Mass: 198.069 Da
• Monoisotopic Mass: 198.069 Da
• Topological Polar Surface Area: 35.500 Ų
• Heavy Atom Count: 14
• Formal Charge: 0
• Complexity: 196.000
• 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 antibody/biological assay protocols apply to this small-molecule building block. For synthetic use, see the Reaction Conditions and Application notes. Analytical protocols typically include:

• Identity/purity check: 1H/13C NMR in CDCl3 or DMSO-d6; GC–MS or LC–MS for mass confirmation.
• Chromatography: Normal-phase silica gel using hexanes/EtOAc gradients; monitor by TLC (UV-active) or HPLC-UV.
• Moisture sensitivity: Not acutely moisture sensitive, but anhydrous handling improves outcomes in base- or acid-catalyzed steps.

Biological Roles

This compound is a synthetic aromatic ester and is not known as a natural metabolite or cofactor.

• General context (literature):
  • Aryl esters can undergo hydrolysis in biological systems to yield the corresponding acids and alcohols; however, rates depend on structure and are highly context-specific.
  • The presence of a methoxy group and a fluorine on the aromatic ring is common in medicinal chemistry for modulating lipophilicity, metabolic stability, and electronic properties. In this case, the molecule serves primarily as a chemical intermediate rather than a probe or bioactive agent per se.
  • No specific enzyme targets or transport roles are associated with ethyl 3-fluoro-2-methoxybenzoate in the literature at large.

Research-use only: Any discussion of biological activity should be restricted to laboratory studies; no clinical or therapeutic claims are made or implied.

Buffer Applications

Not typically applicable. Ethyl 3-fluoro-2-methoxybenzoate is a neutral, hydrophobic aromatic ester and is not used as a buffering agent. For aqueous work, focus on its solubility/partitioning behavior and potential hydrolysis under basic or acidic buffer conditions if present incidentally.

Green Alternatives

• Greener solvent choices for typical transformations (general guidance):

  • Workups and extractions: Prefer EtOAc or MTBE over DCM/chloroform when feasible; both are less hazardous and allow efficient phase separation.
  • Reactions: Replace chlorinated solvents with 2-MeTHF, CPME, or toluene for many steps (reduction, DoM quench, couplings). Consider MeCN or ethanol where polarity and proticity are beneficial.
  • Bases: For saponification, aqueous ethanol or methanol at ambient or slightly elevated temperature reduces energy demand relative to prolonged reflux.

• Comparison snapshot (general, literature-based):

  • DCM vs EtOAc: EtOAc is biodegradable, lower toxicity; however, DCM offers superior solubility for some aryl esters and easier evaporation. Choose EtOAc when chromatographic resolution and solubility allow.
  • THF vs 2-MeTHF: 2-MeTHF is bio-based, higher boiling, forms fewer peroxides, and facilitates phase separation in some cases; THF remains superior for low-temperature organolithium work due to better solvation.
  • Toluene vs CPME: CPME provides hydrophobicity with improved safety profile (lower peroxide formation than ethers like diethyl ether) and supports water-tolerant conditions.

• Process-intensification ideas:

  • Enzymatic ester hydrolysis or transesterification (lipases) in green solvents or solvent-free systems can reduce waste and milder conditions.
  • Flow chemistry for hazardous steps (e.g., lithiation) to minimize solvent and improve heat/mass transfer.

Note: Selection must balance green metrics with reaction performance, safety, and downstream purification.

Pharmaceutical Uses

• Item-specific regulatory status: Not specified for this item; refer to CoA/Spec Sheet. No pharmacopeial monograph is implied.

• General role in pharmaceutical R&D/manufacturing (no therapeutic claims):

  • Intermediate: Useful as a building block to access 3-fluoro-2-methoxybenzoic acid and its amide/ester derivatives, common motifs in medchem for tuning potency and ADME.
  • Protecting/latent functionality: The ethyl ester functions as a protecting group for the acid, enabling transformations incompatible with the free acid (e.g., certain couplings or halogenations). Late-stage hydrolysis provides the acid for salt formation or amide coupling.
  • Impurity profiling: When used in process routes, typical impurities include transesterification byproducts, hydrolysis-derived acid/alcohol, and positional isomers. Appropriate analytical controls (HPLC/GC, NMR) are recommended.
  • Formulation context: As a hydrophobic small molecule, not used as an excipient; it may appear as a process intermediate only. Any residual presence in APIs would be a process-related impurity subject to ICH limits.

Always verify impurity carryover, residual solvents, and identity via batch CoA and applicable internal specifications.

Physical Properties

• Item-specific specifications (from Product Data):

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed values (for reference; not item specifications):

  • Estimated molecular formula (structure-derived): C10H11FO3
  • Estimated molecular weight: ~198.19 g/mol
  • Physical state: Aromatic ethyl benzoate esters with similar substitution are typically colorless to pale liquids or low-melting solids (literature, general trend).
  • Volatility: Expected to be low-to-moderate; benzoate esters commonly have boiling points in the 210–250 °C range (literature, class trend). Exact BP for this specific compound not found at time of writing.
  • Solubility: Generally low water solubility; good solubility in common organic solvents (EtOAc, DCM, THF, toluene, hexanes) typical for substituted ethyl benzoates (literature, class trend).
  • LogP: Aryl esters with one methoxy and one fluoro substituent are typically moderately lipophilic (literature, class trend). No measured logP identified.
  • Refractive index, density, UV cutoff: Not found in public literature for this exact structure at time of writing.

Note: For quantitative specifications (bp, mp, density, UV profile, metals, water, stabilizers), consult the product’s CoA/Spec Sheet. Do not treat the above literature trends as specifications.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

• Stabilizers/inhibitors: Not specified for this item; refer to CoA/Spec Sheet.

• General notes on quality for aromatic building blocks:

  • Typical quality indicators: Identity (1H/13C NMR, MS), purity by HPLC/GC, residual solvents, water (KF), and, where relevant, metal content. For chromatography or photochemical work, low UV-absorbing impurities are important though aromatic esters themselves absorb in the UV.
  • If offered as “research grade,” materials are intended for laboratory R&D. For sensitive applications (medchem SAR, catalysis screening), review trace impurity profiles on the CoA.
  • If high-purity specifications are critical (e.g., ≥98% by HPLC/GC), verify batch-specific values. For reactions sensitive to acid/base, check acidity/alkalinity and residual acid/base impurities.
  • Stabilizer implications: While many benzoate esters are stable without additives, some suppliers include trace acid scavengers or antioxidants. Presence/absence affects downstream reactions (e.g., base-catalyzed steps). Confirm on CoA/Spec Sheet.
  • Documentation: Batch CoA should list analytical methods, acceptance criteria, and results. Request NMR spectra upon need for structural verification.

Conclusion: In absence of explicit grade/purity listing here, rely on the CoA/Spec Sheet for definitive quality attributes and suitability for your use case.

Reaction and Applications

As a substituted ethyl benzoate bearing –OMe (ortho) and –F (meta), this molecule serves as a versatile aromatic building block.

• Transformations of the ester (literature/general):

  • Hydrolysis (saponification) to 3-fluoro-2-methoxybenzoic acid using aq. NaOH or KOH in EtOH/H2O; subsequent acidification affords the acid for amide couplings (EDC/HOBt, HATU) or acid chlorides (SOCl2, oxalyl chloride).
  • Transesterification to alternative alkyl esters (Me, iPr, tert-Bu via isobutylene/H2SO4 or Boc anhydride routes) for protecting group strategy optimization.
  • Reductions: DIBAL-H can furnish the corresponding aldehyde at low temperature; LiAlH4 or BH3·THF gives the benzyl alcohol (3-fluoro-2-methoxybenzyl alcohol) in a single step.

• Aromatic functionalization strategy:

  • Electrophilic aromatic substitution: –OMe strongly directs to positions ortho/para relative to itself. The substitution pattern leaves specific positions (e.g., C5/C6 relative to carbonyl) accessible for nitration, halogenation, or Friedel–Crafts acylation under controlled conditions; note that the ester is deactivating and not compatible with strongly Lewis-acidic FC conditions without protection.
  • Directed ortho metalation (DoM): The methoxy group can enable ortho-lithiation (e.g., s-BuLi/TMEDA, −78 to −40 °C) at the remaining ortho site; subsequent quench with electrophiles (D2O, DMF, I2, B(OMe)3, etc.) installs new functionality.
  • C–F activation: Aryl fluorides are challenging; however, advanced Ni- or Fe-catalyzed borylation/defluorinative coupling methods have been reported for activated substrates (literature). Feasibility should be evaluated case-by-case.

• Cross-coupling approaches:

  • After installing a handle (e.g., Ar–Br/I via halogenation post-DoM), apply Suzuki–Miyaura, Buchwald–Hartwig, or Sonogashira couplings to elaborate the scaffold.

• Applications:

  • Medchem/agrochem intermediate for SAR around anisyl/fluoro motifs; ester serves as a latent acid for late-stage diversification.

Reaction Conditions

General literature guidance for transformations of ethyl 3-fluoro-2-methoxybenzoate or close analogs (verify and optimize in your lab):

• Saponification to acid:

  • Conditions: 1–2 M NaOH or KOH in EtOH/H2O (3:1 to 1:1), 50–80 °C, 2–6 h.
  • Workup: Cool, remove EtOH, acidify to pH ~2 with HCl, extract with EtOAc, dry, concentrate.
  • Typical yields: Good to excellent for benzoate esters.

• DIBAL-H reduction to aldehyde:

  • Solvent: Dry toluene or CH2Cl2; 0 to −78 °C depending on selectivity.
  • Stoichiometry: 1.1–1.3 equiv DIBAL-H; quench with MeOH then Rochelle’s salt.
  • Outcome: Formation of 3-fluoro-2-methoxybenzaldehyde analogue; avoid warming before quench to prevent over-reduction.

• LAH or BH3·THF reduction to benzyl alcohol:

  • Solvent: Anhydrous THF/ether; 0–25 °C to reflux depending on reagent.
  • Quench: Careful, controlled addition of water/isopropanol, then aqueous workup.

• Directed ortho metalation (DoM):

  • Base: s-BuLi (1.1–1.5 equiv) ± TMEDA in dry THF/Et2O at −78 to −40 °C, 0.5–2 h.
  • Electrophile: CO2 (g), DMF, I2, B(OMe)3, ClP(O)(OEt)2, etc.
  • Note: Regioselectivity governed by –OMe; ensure low temperature and anhydrous conditions.

• Electrophilic halogenation (example):

  • NBS (1.05 equiv) with catalytic AIBN or benzoyl peroxide in CCl4 or greener alternatives (MeCN) under light/heat; monitor to avoid over-bromination.

• Cross-coupling (after installing a halide/boronate):

  • Suzuki–Miyaura: Pd(dppf)Cl2 (1–3 mol%), K2CO3 or Cs2CO3, dioxane/H2O or toluene/EtOH/H2O, 50–90 °C.
  • Buchwald–Hartwig: Pd2(dba)3 or Pd(OAc)2, BINAP/XPhos ligands, NaOtBu, toluene/PhMe, 80–110 °C.

All conditions are literature-style guidance for analogous systems; optimize for this substrate.

Safety and Handling

• Item-specific hazard information (Product Data):

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

• General safety guidance for aromatic esters (literature/standard practice; not product-specific):

  • Likely hazards: May cause skin/eye irritation and respiratory irritation if mist or vapors are generated. Avoid inhalation, ingestion, and contact with skin/eyes.
  • PPE: Use lab coat, safety glasses or face shield, and appropriate chemical-resistant gloves (e.g., nitrile). Work in a fume hood to control vapors/aerosols.
  • Handling: Avoid sources of ignition. Prevent prolonged exposure to air/heat that could promote slow hydrolysis or oxidation. Keep containers tightly closed.
  • Incompatibilities: Strong bases and nucleophiles can saponify the ester; strong acids can catalyze transesterification/hydrolysis. Powerful oxidants may react with aromatic organics.
  • First aid (overview; defer to SDS): If on skin/eyes, rinse with water for at least 15 min; remove contaminated clothing. If inhaled, move to fresh air. If swallowed, rinse mouth; seek medical attention in all cases of significant exposure.
  • Spill response: Absorb with inert material (vermiculite, sand), collect for disposal. Ventilate area; avoid release to the environment.

Always consult the SDS for authoritative, product-specific hazard and response information.

Solvent Selection

This product is an aromatic ester building block, not itself a routine laboratory solvent. Solvent selection pertains to its use in synthesis, purification, and analysis.

• Polarity/miscibility context (literature/class trends):

  • Expected to dissolve well in moderately polar aprotic solvents (EtOAc, THF, DCM, MeCN) and in less polar media (toluene, MTBE, hexanes to varying degrees). Poor aqueous solubility.
  • For chromatography: Normal-phase silica using hexanes/EtOAc or hexanes/DCM gradients typically provides good separation. Reverse-phase (C18) with MeCN/H2O + 0.1% acid may be used analytically; compound retention likely moderate-to-strong due to hydrophobicity.

• When to choose specific solvents:

  • Base-catalyzed saponification: EtOH/H2O or MeOH/H2O mixtures improve miscibility while maintaining ester hydrolysis rates.
  • Transesterification: Anhydrous MeOH, EtOH, or 2-PrOH with catalytic acid/base; remove product alcohol by distillation to drive equilibrium.
  • Reductions (DIBAL-H, LiAlH4): Use dry toluene/CH2Cl2 (DIBAL-H) or dry ether/THF (LiAlH4) under inert atmosphere.
  • Ortho-metalation on the anisyl ring: Dry THF or diethyl ether at low temperature under N2/Ar.

• Small comparison (general):

  • DCM vs EtOAc: DCM offers higher solubility and easier workup; EtOAc is greener and often adequate.
  • Toluene vs THF: Toluene favors higher-temperature operations; THF enables low-temperature organometallic chemistry.

Always verify solvent compatibility with your specific transformation and safety constraints.

Storage and Reconstitution

• Item-specific storage (Product Data):

  • Storage Conditions: Room temperature.
  • Shipped In: Not specified for this item; refer to CoA/Spec Sheet.

• General storage guidance (aromatic esters):

  • Keep tightly sealed in an amber or opaque container to limit light exposure; store under inert gas if long-term storage is planned to minimize slow hydrolysis/oxidation.
  • Avoid prolonged exposure to moisture and strong bases/acids. Store away from incompatible reagents (strong oxidizers, strong nucleophiles).
  • If solidification/crystallization occurs upon cold storage, gently warm to room temperature to re-liquefy before use (if applicable). No reconstitution is typically required; use as supplied.
  • For analytical reliability, allow to equilibrate to room temperature before opening to prevent moisture condensation.

• Shelf life and QC:

  • Inspect periodically by TLC/HPLC for signs of hydrolysis (appearance of acid/alcohol). If impurities increase, purify by distillation under reduced pressure or column chromatography as appropriate.

For definitive storage and handling directions, consult the product label and CoA/Spec Sheet. Research use only.

Structure and Identity

Brief overview: Ethyl 3-fluoro-2-methoxybenzoate is an ortho-methoxy, meta-fluoro substituted ethyl benzoate ester, useful as an aromatic building block.

• Item-specific (Product Data):

  • SKU: E948488
  • CAS: 1106304-72-6
  • PubChem CID: 44203154
  • InChIKey: 305618 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/computed identity (for reference only; verify before use):

  • Typical molecular formula (derived from name): C10H11FO3 (literature/structure-derived)
  • Typical molecular weight: ~198.19 g/mol (literature/structure-derived)
  • Representative SMILES: CCOC(=O)c1c(OC)c(F)cccc1 (literature/structure-derived)
  • 2D structural description: A benzene ring bearing an ethyl benzoate ester at C1 (–C(=O)OCH2CH3), an ortho methoxy group at C2 (–OCH3), and a meta fluoro substituent at C3 (–F); remaining ring positions are hydrogen.

• Structural features and reactivity implications (general):

  • Functional groups: aromatic ester (benzoate), aryl methoxy ether, aryl fluoride.
  • Directing effects: –OMe is a strong ortho/para director; –CO2Et is meta-directing and deactivating; –F is deactivating but ortho/para directing via resonance. The substitution pattern provides a differentiated aromatic scaffold for regioselective transformations.
  • Stereochemistry: Achiral, planar aromatic core.

Synthetic Utility

• Functional group leverage:

  • Ester: Platform for hydrolysis to acid, conversion to acid chlorides, amide formation, Curtius/Schmidt pathways from the acid, selective reductions (DIBAL-H to aldehyde; LAH/BH3 to alcohol), and transesterifications.
  • Methoxy: Electron-donating/activating for EAS, handle for demethylation (e.g., BBr3) to reveal a phenol if needed after orthogonal protection strategies.
  • Fluoro: Modulates electronics and blocking group; can participate in advanced defluorinative couplings or serve as a bioisostere placeholder in medchem SAR.

• Retrosynthetic value:

  • Serves as a convergent node: One branch elaborates the aromatic core via DoM/EAS; the other transforms the ester to introduce sidechains or amide-linked pharmacophores.
  • Orthogonal reactivity: The ester tolerates many catalytic C–H/C–X activation conditions; the methoxy group directs ortho metalation, enabling regioselective installation of boron/halogen/aldehyde handles for subsequent cross-couplings.

• Named/representative tactics (literature):

  • DoM with s-BuLi/TMEDA, quench with B(OMe)3 to give aryl boronic esters, then Suzuki–Miyaura coupling.
  • Electrophilic halogenation (NBS/NIS) at activated positions followed by Buchwald–Hartwig amination or Sonogashira alkynylation.
  • Ester hydrolysis then HATU/HOAt-mediated amide coupling for rapid library generation.

• Compatibility notes:

  • Avoid strong bases/acids when preserving the ester. For FC-type acylations, protect or replace the ester functionality to prevent cleavage.
  • Methoxy demethylation conditions (BBr3, AlCl3/thiols) may also affect the ester; stage appropriately.

Target Specificity

Not applicable. This product is a small-molecule chemical building block and is not an antibody, protein, or biological probe with defined target specificity. No antigen, epitope, clone, isotype, or species reactivity information applies.