Ethyl 3-fluoro-6-iodo-2-methylbenzoate - ≥95% , CAS No.1417190-32-9

CAS: 1417190-32-9 Cat. No.: E190872 분자식: C₁₀H₁₀FIO₂ 분자량: 308.09

GRADE & PURITY ≥95%

Storage

Room temperature

Shipped In

Normal

Specifications

사양 및 순도

≥95%

보관 조건

Room temperature

배송

Normal

순수함

≥95%

이름과 식별자

정식 스마일

CCOC(=O)C1=C(C=CC(=C1C)F)I

IUPAC Name

ethyl 3-fluoro-6-iodo-2-methylbenzoate

InChIKey

CKYMMECDQSWSOE-UHFFFAOYSA-N

INCHI

1S/C10H10FIO2/c1-3-14-10(13)9-6(2)7(11)4-5-8(9)12/h4-5H,3H2,1-2H3

이성체 SMILES

CCOC(=O)C1=C(C=CC(=C1C)F)I

분자량

308.09

Reaxy-Rn

23235663

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=23235663&ln=

화학 및 물리적 특성

• 분자량: 308.090 g/mol
• XLogP3: 3.300
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 3
• Exact Mass: 307.971 Da
• Monoisotopic Mass: 307.971 Da
• Topological Polar Surface Area: 26.300 Ų
• Heavy Atom Count: 14
• Formal Charge: 0
• Complexity: 210.000
• 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

Not applicable.

• No validated bioassay protocols (WB, IHC, IF, FC) are associated with this small-molecule building block. For synthetic procedures, see Reaction Conditions for general literature setups. Project-specific SOPs should be developed and validated in-house.

Biological Roles

Applicability

• This material is a synthetic organic building block with no known intrinsic biological role.

General context (literature; not product-specific claims)

• Aromatic esters like benzoates can be precursors to probes or ligands after further functionalization (e.g., coupling at the aryl iodide, then converting the ester to amides). The aryl fluoride is typically retained throughout synthetic sequences, offering a site for later modification or for modulating physicochemical properties (e.g., lipophilicity, metabolic stability) in discovery chemistry.

Notes

• Any use in biological assays should be as a research intermediate or as part of structure–activity relationship (SAR) exploration after additional transformations. Research use only; not for diagnostic or therapeutic applications.

Buffer Applications

Not typically applicable.

• This compound is a hydrophobic organic substrate and does not function as a buffering agent. For aqueous biological work, prepare solutions in water-miscible organic co-solvents (e.g., DMSO) before dilution, if needed for assay development after further derivatization.
• See Solvent Selection and Reaction & Applications for the most relevant guidance.

Green Alternatives

Greener choices focus on solvent/catalyst/base selection rather than replacing the substrate itself.

Opportunities (literature-guided; balance performance vs sustainability)

• Solvents for Pd-catalyzed couplings:
  • Replace 1,4-dioxane/DMF with 2-MeTHF, CPME, or ethanol/water when compatible with the catalyst system.
  • Use aqueous micellar catalysis (e.g., TPGS-750-M) to run Suzuki or Buchwald–Hartwig couplings in water at low catalyst loadings.
• Bases and additives:
  • Favor inorganic carbonates/phosphates over strong organic bases to reduce hazards and facilitate workup.
• Energy and process:
  • Room-temperature or mild-temperature couplings are feasible with modern ligand systems on aryl iodides, reducing energy input.

Illustrative comparison (general; not product specifications)

• 1,4-Dioxane: petroleum-derived; probable carcinogen concerns; excellent solvating power for Pd-catalysis.
• 2-MeTHF: biorenewable from hemicellulose; good for organometallics; water removal may be needed.
• Ethanol/water: green, low toxicity; may limit solubility of hydrophobic partners—use phase-transfer or surfactants.
• Micellar water: minimal organic solvent; requires specialized surfactants and catalyst systems.

Practical tip

• Because the Ar–I bond is highly reactive, greener media often still deliver good conversions—screen catalysts/ligands (e.g., XPhos, SPhos, BrettPhos families) under ethanol/water or 2-MeTHF before defaulting to dioxane/DMF.

Pharmaceutical Uses

Applicability

• Not an excipient or approved additive. Research use only.

General formulation/manufacturing context (literature; not product-specific claims)

• As a benchtop intermediate, this aryl iodide benzoate may serve in the synthesis of advanced intermediates toward candidate molecules. The ethyl ester can be converted to acids, amides, and alcohols—functionalities commonly incorporated in small-molecule discovery libraries.
• No pharmacopeial monograph is expected for this highly specific substituted benzoate. Any GMP relevance would require project-specific qualification, impurity profiling, and residual solvent/metal controls according to ICH guidelines.

Practical tips

• If used in route scouting for API development, ensure robust analytical methods (qNMR, HPLC area%, ICP-MS for Pd/Cu residues post-coupling) and define purge strategies for halide/metal impurities during scale-up.

Physical Properties

Item-specific (Product Data)

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

Computed/literature (informational; not product specifications)

• Approximate molecular weight: ~308.09 g/mol (computed from C10H10FIO2, see Structure & Identity).
• Physical state: Aromatic ethyl benzoates of similar substitution are typically low-melting solids or viscous oils (literature generalization). Actual state for this item is not specified; refer to CoA.
• Solubility (qualitative, literature expectation): good solubility in nonpolar to moderately polar organic solvents (e.g., dichloromethane, chloroform, toluene, THF, ethyl acetate); negligible solubility in water.
• Density, refractive index, melting/boiling points, UV cutoff, vapor pressure, logP, pKa: Not specified for this item; refer to CoA/Spec Sheet. If required for method development, determine experimentally or consult primary literature for close analogs.

General guidance for handling as a substrate

• The aryl iodide and ester functionalities are thermally stable under typical laboratory conditions. Avoid prolonged heating above typical ester stability limits and avoid moisture/strong base if ester preservation is desired.

Quality and Grades

Item-specific (Product Data)

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

Guidance for this compound class (general; not product specifications)

• For cross-coupling and downstream medicinal chemistry, impurities such as hydrolyzed acids, dehalogenated arenes, or residual halide salts can impact reaction rates and selectivity. Review the supplied CoA (HPLC/GC purity, water content) prior to use in critical steps.
• If UV-based analytics (HPLC/UPLC) are used, typical benzoate chromophores have strong absorbance in the near-UV, aiding detection; low-UV “HPLC grade” solvent requirements apply to mobile phases rather than to this substrate.
• Stabilizers: None are typically required for aryl iodide benzoates. If any stabilizer is present, it will be stated on the CoA; absence of such a note generally implies neat material.
• Batch-to-batch control: For scale-up, verify halogen content (e.g., by HRMS or elemental analysis) to ensure no partial deiodination. Confirm identity by 1H/13C NMR, and consider 19F NMR for the fluorine substituent; the C–I bearing carbon often appears downfield in 13C NMR (useful diagnostic).
• Recommendation: For sensitive couplings, pre-test a small reaction with your catalyst system to confirm performance with the supplied lot.

Reaction and Applications

Core use: versatile aryl iodide/benzoate building block for cross-coupling, late-stage diversification, and functional-group interconversions.

Key reaction families (literature examples; general guidance)

• C–C cross-coupling on Ar–I:
  • Suzuki–Miyaura with aryl/alkenyl/alkyl boron reagents; bases such as K2CO3, K3PO4, Cs2CO3; Pd(0/II) catalysts. The iodo substituent provides high reactivity and orthogonal selectivity vs the aryl fluoride (F remains intact).
  • Sonogashira coupling with terminal alkynes (Pd/Cu co-catalysis or copper-free protocols), enabling facile access to aryl alkynes.
  • Heck reaction with alkenes to give vinylarenes; the ester tolerates typical conditions.
• C–N and C–O bond formation:
  • Buchwald–Hartwig amination on the aryl iodide to introduce anilines; oxygenation to aryl ethers via Ullmann-type or Pd-catalyzed coupling (depending on conditions).
• Halogen–lithium exchange and metalation:
  • Rapid exchange at C–I using n-BuLi or t-BuLi at −78 °C in THF affords the corresponding aryllithium for electrophile trapping (e.g., formylation, borylation). The ester requires care to avoid nucleophilic attack; use steric/electrophile control or directed strategies.
• Ester transformations:
  • Saponification to the 3-fluoro-6-iodo-2-methylbenzoic acid, followed by amide coupling (EDC/HOBt, HATU) or conversion to acid chlorides (SOCl2, oxalyl chloride).
  • Reductions: DIBAL-H to the corresponding benzyl alcohol (via aldehyde at −78 °C) or LiAlH4 to the primary alcohol; selectivity control is crucial to avoid C–I reduction.

Synthetic context

• Orthogonal handles (I vs F vs CO2Et) enable stepwise diversification—couple at I, then manipulate the ester, leaving C–F untouched for additional late-stage chemistry.

Reaction Conditions

General literature conditions for aryl iodides (guidance only; optimize per substrate/partner)

• Suzuki–Miyaura coupling

  • Catalyst: Pd(PPh3)4 (1–3 mol%) or Pd2(dba)3/XPhos-type ligands.
  • Base: K2CO3, K3PO4, or Cs2CO3 (2–3 equiv).
  • Solvent: 1,4-dioxane/H2O (3:1), 2-MeTHF/H2O, or EtOH/H2O.
  • Temperature: 25–80 °C; aryl iodides often react at lower temperatures than bromides/chlorides.
  • Notes: Maintain ester integrity by avoiding strong aqueous base at elevated temperatures for extended times.

• Sonogashira coupling

  • Catalyst: Pd(PPh3)2Cl2 (1–2 mol%) with CuI (2–5 mol%); or copper-free systems with bulky phosphines.
  • Base/Solvent: Et3N or iPr2NEt as base/solvent; or THF/Et3N mixtures.
  • Temperature: rt to 60 °C. Degas solvents; exclude moisture for sensitive alkynes.

• Buchwald–Hartwig amination

  • Catalyst: Pd2(dba)3 with BrettPhos/SPhos (1–3 mol% Pd); precatalysts (e.g., XPhos Pd G3) convenient.
  • Base: NaOtBu, Cs2CO3.
  • Solvent: toluene, 2-MeTHF, or dioxane.
  • Temperature: 60–100 °C.

• Halogen–lithium exchange (on Ar–I)

  • Reagent: n-BuLi or t-BuLi (1.1–1.5 equiv).
  • Solvent/Temp: anhydrous THF, −78 °C; fast exchange. Quench with electrophiles (e.g., B(OMe)3, DMF).
  • Caution: Competitive addition to the ester carbonyl is possible—use appropriate protection or conditions.

• Ester chemistry

  • Saponification: K2CO3/KOH in MeOH/H2O or THF/H2O, 0–25 °C.
  • Reduction: DIBAL-H (−78 to −20 °C) for aldehyde/alcohol; LiAlH4 (0–25 °C) to alcohol (risk of C–I reduction—monitor).

Yields: Dependent on partners and conditions; aryl iodides commonly afford high conversions under optimized protocols (literature).

Safety and Handling

Item-specific (Product Data)

• GHS classification: Not specified for this item; refer to SDS.
• Signal word / H-statements / Pictograms: Not specified for this item; refer to SDS.
• Storage conditions: Room temperature (as provided). Ship under normal conditions.

General safety guidance (literature/institutional best practices; consult SDS for authoritative details)

• Likely hazards: Aromatic esters and aryl iodides are commonly classified as irritants; handle as harmful if swallowed/inhaled and as skin/eye irritants until specific SDS indicates otherwise.
• PPE: lab coat, safety glasses or face shield, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a fume hood to minimize inhalation exposure.
• Incompatibilities: Strong bases/acids (can hydrolyze the ester); strong nucleophiles (transesterification/saponification); powerful reducing agents that may induce dehalogenation; strong oxidants (combustible organic).
• Special risks: None unique beyond typical organic halides; aryl iodides do not form peroxides. Avoid high-temperature distillation if material is a viscous oil—prefer short-path at reduced pressure if purification is required.
• First-aid overview: Eye/skin contact—flush with water for 15 minutes, remove contaminated clothing. Inhalation—move to fresh air; seek medical attention if symptoms persist. Ingestion—rinse mouth; do not induce vomiting; seek medical attention. Always follow the specific SDS.
• Spill/cleanup: Absorb with inert material (vermiculite), place in suitable waste container. Prevent entry to drains. Dispose of according to institutional and regulatory requirements.

Solvent Selection

Applicability

• This product is a synthetic substrate, not a solvent. Solvent selection pertains to its dissolution and to reaction media.

General solubility/miscibility guidance (literature-based)

• Expected to dissolve well in dichloromethane, chloroform, THF, 2-MeTHF, ethyl acetate, acetone, acetonitrile, toluene, and DMF/DMSO. Poorly soluble in water.
• Polarity: Moderately lipophilic aromatic ester bearing heavy halogens; favors nonpolar to mid-polar aprotic media.

Choosing a solvent by application

• Cross-coupling (Suzuki/Sonogashira): 1,4-dioxane/water, toluene, 2-MeTHF, or ethanol/water mixtures are common. For green emphasis, prefer aqueous ethanol or 2-MeTHF when catalyst/base system allows.
• Nucleophilic substitutions on the ester (transesterification/saponification): methanol/ethanol (alcoholysis) or mixed aqueous-organic (THF/H2O, MeOH/H2O) for base hydrolysis.
• Reductions (e.g., LiAlH4, DIBAL): Etheral solvents (THF, Et2O) for LiAlH4; toluene or CH2Cl2 for DIBAL.
• Halogen–lithium exchange or directed metalation: anhydrous THF or Et2O at cryogenic temperatures.

Small comparison (general)

• 1,4-Dioxane: excellent for Pd-catalysis but with sustainability concerns.
• 2-MeTHF: greener, good for organometallics and many couplings; water content must be managed.
• Toluene: non-polar, thermally robust; may limit base solubility.
• DMF/DMSO: high polarity for difficult dissolutions; consider workup challenges and safety profiles.

Storage and Reconstitution

Item-specific (Product Data)

• Storage conditions: Room temperature.
• Shipped in: Normal conditions.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.

General handling and solution preparation (guidance)

• Keep container tightly closed under inert atmosphere if long-term storage is planned, especially after opening, to minimize moisture ingress and potential ester hydrolysis.
• If solidified or viscous, gently warm to ambient temperature to aid handling. Avoid prolonged heating.
• Working solutions: Prepare in dry organic solvents (e.g., DMSO, THF, CH2Cl2, toluene, acetonitrile) as needed for reactions. For analytical stock solutions, DMSO or acetonitrile are common—store at 2–8 °C and use within 1–2 weeks, or aliquot and freeze to avoid repeated freeze–thaw.
• Reconstitution: Not applicable to neat chemicals; if a weighed solid, dissolve to desired concentration in a compatible, anhydrous solvent immediately prior to use.
• Stability: Aromatic esters and aryl iodides are generally stable at room temperature away from light. For extended storage, protect from light to minimize any potential photolytic dehalogenation.

Disposal

• Dispose of wastes and rinse solvents as halogenated organic waste per institutional and regulatory guidelines.

Research use note

• For research use only. Not for human or veterinary use.

Structure and Identity

Item-specific (Product Data)

• SKU: E190872
• Product name: Ethyl 3-fluoro-6-iodo-2-methylbenzoate
• CAS: 1417190-32-9
• InChIKey: 46948 (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.

Computed/literature (informational; not product specifications)

• Estimated molecular formula from name: C10H10FIO2 (computed)
• Estimated molecular weight: ~308.09 g/mol (computed from C10H10FIO2)
• Structural features: benzoate ethyl ester core (–CO2Et) at the 1-position; ortho methyl at C2; meta fluoro at C3; iodo at C6. Functional groups include an aryl iodide (highly cross-coupling-active), an aryl fluoride (electron-withdrawing, C–F bond robust), and an ethyl ester (hydrolyzable/derivatizable).
• 2D description: a substituted benzene ring bearing an ethyl benzoate group (–C(=O)OCH2CH3) at C1; CH3 at C2 (ortho); F at C3 (meta); I at C6 (para to C3, ortho to C1).

General notes

• Stereochemistry: none (achiral).

Synthetic Utility

Functional handles and orthogonality

• Aryl iodide (C–I): highest reactivity among aryl halides for Pd-catalyzed cross-couplings (Suzuki, Sonogashira, Heck, Buchwald–Hartwig). Allows transformations under milder conditions, preserving sensitive motifs.
• Ethyl ester (–CO2Et): convertible via saponification, transesterification, or selective reduction. Provides a handle for amide diversification after hydrolysis.
• Aryl fluoride (C–F): robust under most coupling conditions; can be engaged later via SNAr if activated, or via metal-catalyzed C–F functionalization using specialized systems.
• Ortho-methyl: influences directing effects and reactivity; can be oxidized (e.g., benzylic oxidation) or functionalized under radical conditions if desired.

Retrosynthetic value

• Serves as a convergent node: perform Ar–I coupling to install complexity, then manipulate the carboxylate function, keeping C–F intact for a tertiary modification step.

Downstream elaborations (examples)

• Borylation at C–I (Pd or Ni catalysis) → pinacol boronate; subsequent Suzuki coupling expands scope.
• Amination at C–I (Buchwald–Hartwig) → anilines; amide formation from the ester-derived acid enables bifunctional targets.
• Sonogashira → aryl alkynes; further cyclizations or hydroarylations accessible.

Selectivity considerations

• Choose catalysts/ligands that are selective for Ar–I over potential ester activation. Employ base and temperature control to avoid saponification when ester integrity is required.

Target Specificity

Not applicable.

• This product is a small-molecule building block, not a biological macromolecule or affinity reagent. No antigen/epitope, clone, or species reactivity data apply.