Ethyl 6-(3,5-difluorophenyl)-6-oxohexanoate , CAS No.898752-40-4

CAS: 898752-40-4 Cat. No.: E936451 분자식: C₁₄H₁₆F₂O₃ 분자량: 270.276 PubChem CID: 24727361

Storage

Room temperature

Specifications

보관 조건

Room temperature

이름과 식별자

• 정식 스마일: CCOC(=O)CCCCC(=O)C1=CC(=CC(=C1)F)F
• IUPAC Name: ethyl 6-(3,5-difluorophenyl)-6-oxohexanoate
• InChIKey: YYQROGWZAYKEAF-UHFFFAOYSA-N
• INCHI: 1S/C14H16F2O3/c1-2-19-14(18)6-4-3-5-13(17)10-7-11(15)9-12(16)8-10/h7-9H,2-6H2,1H3
• 이성체 SMILES: CCOC(=O)CCCCC(=O)C1=CC(=CC(=C1)F)F
• PubChem CID: 24727361
• 분자량: 270.276

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic oxygen compounds
    • 분류 Organooxygen compounds
      • Subclass Carbonyl compounds
        • Level5 Ketones
          • Level6 Aryl ketones
            • Level7 Phenylketones
              • Level8 Alkyl-phenylketones

• Kingdom: Organic compounds
• Superclass: Organic oxygen compounds
• 분류: Organooxygen compounds
• Subclass: Carbonyl compounds
• Intermediate Tree Nodes: Ketones - Aryl ketones - Phenylketones
• Direct Parent: Alkyl-phenylketones
• Alternative Parents: Butyrophenones Benzoyl derivatives Aryl alkyl ketones Fluorobenzenes Fatty acid esters Aryl fluorides Carboxylic acid esters Monocarboxylic acids and derivatives Organofluorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Alkyl-phenylketone - Butyrophenone - Benzoyl - Aryl alkyl ketone - Halobenzene - Fluorobenzene - Fatty acid ester - Aryl fluoride - Benzenoid - Monocyclic benzene moiety - Aryl halide - Fatty acyl - Carboxylic acid ester - Monocarboxylic acid or derivatives - Carboxylic acid derivative - Organofluoride - Organohalogen compound - Organic oxide - Hydrocarbon derivative - Aromatic homomonocyclic compound
• 설명: This compound belongs to the class of organic compounds known as alkyl-phenylketones. These are aromatic compounds containing a ketone substituted by one alkyl group, and a phenyl 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

화학 및 물리적 특성

• 분자량: 270.270 g/mol
• XLogP3: 2.600
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 8
• Exact Mass: 270.107 Da
• Monoisotopic Mass: 270.107 Da
• Topological Polar Surface Area: 43.400 Ų
• Heavy Atom Count: 19
• Formal Charge: 0
• Complexity: 297.000
• 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 immunoassay or bioassay protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule building block. For synthetic protocols, see Reaction Conditions and Synthetic Utility sections.

Biological Roles

This product is an organic synthetic intermediate and does not have an inherent biological role.

• General context (for chemists working in life-science discovery)

  • The 3,5-difluorophenyl motif is widely used in medicinal chemistry to modulate lipophilicity, metabolic stability (blocking oxidative metabolism at the ring), and conformational preferences. Such effects are system-dependent and require empirical validation.
  • The 1,6-dicarbonyl handle enables rapid scaffold diversification, which is advantageous for SAR campaigns (e.g., generating rings, keto-alcohols, keto-amides).

• No biological/biochemical function is assigned to this specific substance. Any use in biological assays should be as a research chemical standard or intermediate under appropriate controls. No medical or clinical claims are made or implied.

Buffer Applications

Not typically applicable. This compound is a hydrophobic organic building block and is not used to prepare aqueous buffer systems. For practical work, select organic solvent systems discussed under Solvent Selection, and use standard laboratory buffers only for workup/washing if needed (keeping contact brief to avoid ester hydrolysis).

Green Alternatives

While this compound is a synthetic building block (not a solvent or reagent per se), greener choices can be made for the media and reagents used with it.

• Solvent choices (greener preferences)

  • Favor 2-MeTHF or CPME over THF/diethyl ether for enolate chemistry when compatible; they often allow similar reactivity with improved safety and renewable sourcing.
  • Use EtOAc or Me-THF instead of DCM for extractions and some reductions where feasible.
  • Employ toluene or anisole as higher-boiling, less toxic aromatics versus chlorinated solvents for thermal steps.

• Reducing/oxidizing agents (greener options, context-dependent)

  • Prefer catalytic hydrogenation over stoichiometric metal hydrides where selectivity allows (reduces waste).
  • For ketone reductions, transfer hydrogenation (e.g., Ru, Ir, or organocatalytic systems with i-PrOH) can be an alternative to borohydrides.

• Comparison snapshot (general)

  • THF vs 2-MeTHF: similar polarity and low-temperature performance; 2-MeTHF is bio-derived, forms fewer peroxides, and facilitates phase-splitting with brine.
  • DCM vs EtOAc: DCM offers superior solvating power for some reductions; EtOAc is biodegradable and less problematic from a regulatory standpoint.

• Process considerations

  • Minimize protecting groups by exploiting intrinsic chemoselectivity (reduce the aryl ketone selectively before ester manipulation).
  • Consider telescoping steps (e.g., enolate formation → intramolecular aldol → dehydration) to reduce solvent swaps and workups.

Pharmaceutical Uses

• Formulation/excipient status: Not applicable. This compound is a research-grade organic intermediate and is not used as a pharmaceutical excipient.

• Relevance to drug discovery (general, non-clinical)

  • The 3,5-difluorophenyl unit is a common motif in discovery chemistry. This building block can be leveraged to introduce that motif while enabling further transformations (e.g., cyclizations, amide couplings) en route to candidate molecules.

• Pharmacopeial status: Not specified for this item; refer to CoA/Spec Sheet if any compendial references exist.

No therapeutic claims are made; for laboratory research use only.

Physical Properties

• From Product Data (item-specific)

  • Appearance: 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 (reference values only; not product specifications)

  • Estimated formula (from name): C15H18F2O3
  • Estimated formula weight: ~284.30 g/mol
  • Expected physical state: oily liquid or low-melting solid typical for aryl-alkyl keto-esters of similar size (literature trend).
  • Solubility profile: expected high solubility in common organic solvents (EtOAc, DCM, THF, MeOH) and very low solubility in water (general behavior of aryl keto-esters).
  • Volatility: low to moderate; aryl ketone/ester functionality typically affords higher boiling points; vacuum may be required for distillation (literature trend).

• General notes for handling (physical behavior)

  • The 1,6-dicarbonyl motif can weakly chelate metals; avoid strong bases in aqueous media if hydrolysis of the ester is a concern.
  • Refractive index, density, UV cutoff, and precise bp/mp: Not specified for this item; refer to CoA/Spec Sheet.

Quality and Grades

• From Product Data

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

• Interpreting grades (general guidance)

  • Research/technical grade materials are generally suitable for synthetic applications, method development, and screening. If your application is chromatography-sensitive (e.g., photochemical steps or trace-metal-catalyzed couplings), request CoA details on residual solvents, water content, and trace metals.
  • For building blocks like aryl keto-esters, UV absorbance and GC/HPLC purity can strongly influence reaction outcomes (e.g., in photoredox or when monitoring by HPLC). If HPLC grade or low-UV specifications are required, please inquire.

• Implications for this item

  • Absence of a declared purity means you should verify suitability for sensitive steps by small-scale trials or by requesting a current CoA.
  • If using in base-catalyzed cyclizations or enolate chemistry, control of acidic/neutral impurities and water is beneficial. Karl Fischer moisture, peroxide content, and specific metal analyses: Not specified for this item; refer to CoA/Spec Sheet.

Reaction and Applications

• Key reactivity (general for this scaffold)

  • 1,6-Dicarbonyl motif: The molecule contains an ethyl ester and a distal aryl ketone. This enables intramolecular aldol condensations (ester enolate attacking the aryl ketone) to access cyclohexanol/ cyclohexenone esters after dehydration and, with subsequent transformations, bicyclic frameworks.
  • Chemoselective reductions: NaBH4 or catalytic hydrogenation can reduce the aryl ketone to a secondary alcohol while leaving the ester intact. Alternatively, DIBAL-H can partially reduce the ester to an aldehyde in the presence of the aryl ketone under controlled conditions.
  • Acyl manipulations: The ester can undergo saponification to the corresponding acid, followed by Curtius/Schmidt for homologations or amide coupling to generate keto-amides retaining the difluorophenyl ketone.
  • Carbon–carbon formation at the ester α-position: Strong bases (LDA, NaHMDS) generate the ester enolate for alkylation, aldol, or Michael additions.

• Application ideas (expansion of typical manufacturer uses for such building blocks)

  • Scaffold diversification in medicinal chemistry: install the 3,5-difluorophenyl pharmacophore while exploring ring closures to generate substituted cyclohexanones.
  • Late-stage arene editing: the 3,5-difluoro motif modulates electronics and lipophilicity; subsequent substitutions typically proceed on the aliphatic portion rather than the ring (fluorides are relatively inert to SNAr in absence of strong activation).
  • Oxidations/functional group interconversions: Baeyer–Villiger oxidation of the aryl ketone to an aryl ester; ketone protection as ketal to enable selective transformations at the ester.

• Practical tips

  • Maintain anhydrous conditions for base-mediated steps; quench carefully to avoid transesterification.
  • Control temperature to achieve chemoselectivity between ester and ketone.

Reaction Conditions

General guidance from literature for molecules bearing an aryl ketone and an ethyl ester separated by a pentamethylene spacer (not item-specific specifications):

• Intramolecular aldol (enolate → aryl ketone)

  • Base: LDA or NaHMDS (1.1–1.5 equiv)
  • Solvent: THF or 2-MeTHF, −78 to 0 C, then warm to rt
  • Time: 1–4 h at low temperature, 2–12 h upon warming
  • Notes: Quench with NH4Cl; dehydration may occur under acidic or basic workup to give enone.

• Chemoselective ketone reduction

  • Reagent: NaBH4 (1.1–2.0 equiv)
  • Solvent: MeOH, EtOH, or i-PrOH, 0–25 C
  • Time: 0.5–3 h
  • Selectivity: Typically reduces the aryl ketone preferentially over the ester.

• Partial ester reduction to aldehyde

  • Reagent: DIBAL-H (1.2–2.0 equiv)
  • Solvent: toluene or CH2Cl2, −78 to −20 C
  • Time: 0.5–2 h
  • Notes: Carefully controlled quench (MeOH, then aqueous Rochelle’s salt).

• Hydrolysis/amidation

  • Saponification: aq. NaOH or KOH (1–2 M), THF/MeOH/H2O, 0–25 C, 1–4 h
  • Coupling: EDC/HOBt, HATU, or DIC/DMAP in DMF or DCM for conversion of acid to amide after hydrolysis.

• Oxidations

  • Baeyer–Villiger: mCPBA (1.5–2.0 equiv) in DCM, 0–25 C; yields aryl ester (migration tendency aryl > alkyl).

Reported yields and exact conditions vary with substrate and scale; optimize empirically.

Safety and Handling

• From Product Data

  • GHS Classification: Not specified for this item; refer to SDS.
  • Signal Word: Not specified for this item; refer to SDS.
  • Hazard Statements: Not specified for this item; refer to SDS.
  • Pictograms: Not specified for this item; refer to SDS.
  • Storage Conditions: Room temperature.
  • Research Use Note: For research use only.

• General laboratory safety guidance (not a substitute for SDS)

  • PPE: lab coat, safety glasses or splash goggles, and appropriate chemically resistant gloves (e.g., nitrile). Work in a fume hood to minimize inhalation of vapors or aerosols.
  • Handling: Avoid contact with strong bases and nucleophiles if ester stability is required; avoid strong oxidants/reductants unless intended for reaction. Prevent prolonged skin contact; avoid inhalation of mists.
  • Incompatibilities (general for esters/aryl ketones): strong bases (saponification), strong acids (acidolysis), and powerful reducing agents (e.g., LiAlH4) which may reduce the ester and/or ketone.
  • First aid (overview): If on skin, wash with soap/water. If in eyes, rinse cautiously with water for several minutes and seek medical advice. If inhaled, move to fresh air. If swallowed, rinse mouth; do not induce vomiting; seek medical attention. Always consult the SDS for definitive measures.
  • Fire safety: Combustible organic; use CO2, dry chemical, or foam extinguishers suitable for organic solvent fires. Maintain good housekeeping to avoid accumulation of flammable vapors.
  • Waste: Collect organic waste in appropriate halogenated/non-halogenated streams per institutional and regulatory requirements.

Solvent Selection

This product is an organic building block rather than a solvent; solvent selection here refers to choosing media for its transformations and handling.

• Polarity/miscibility considerations (general)

  • Expected to dissolve well in moderately polar aprotic solvents (DCM, THF, EtOAc, MeCN) and many nonpolar aromatics (toluene). Water solubility expected to be very low.

• Choosing a solvent by operation

  • Workup/extraction: EtOAc/hexanes or DCM/brine systems are typical; avoid prolonged basic aqueous contact to minimize ester hydrolysis.
  • Enolate chemistry at the ester α-position: THF, MTBE, or toluene with LDA/NaHMDS at −78 to 0 C for strong control of chemoselectivity (literature practice).
  • Chemoselective ketone reduction (NaBH4): MeOH, EtOH, or i-PrOH at 0–25 C commonly reduce aryl ketones faster than aliphatic esters (literature).
  • DIBAL-H partial reduction of the ester: toluene or CH2Cl2 at −78 to −20 C to target the aldehyde while preserving the aryl ketone (literature).

• Small comparison (general)

  • THF: excellent for strong bases and low-temperature enolization; may require peroxide testing after long storage (solvent property).
  • DCM: great for chemoselective reductions and acylations; easy removal; low boiling.
  • Toluene: good for thermal cyclizations and DIBAL reductions; higher boiling for elevated temperatures.

Storage and Reconstitution

• From Product Data

  • Storage Conditions: 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.

• Practical guidance (general)

  • Store tightly closed under an inert atmosphere (e.g., nitrogen) if long-term storage is anticipated, to minimize adventitious hydrolysis or oxidation.
  • Protect from strong light and moisture. Keep in a cool, dry place; avoid temperature cycling.
  • If solid, warm gently to room temperature and homogenize before sampling. If an oil, use a dry syringe or spatula in a fume hood.
  • Reconstitution/dissolution: Readily dissolves in common organic solvents such as DCM, EtOAc, THF, MeOH, or toluene (general behavior for aryl keto-esters). Filter through a PTFE syringe filter if particulate is present.
  • Freeze–thaw: Typically not sensitive, but if formulating stock solutions, aliquot and store at recommended conditions to avoid repeated freeze–thaw cycles that may introduce moisture.

For definitive handling and storage instructions, consult the product’s CoA and SDS. For research use only.

Structure and Identity

Brief: Ethyl 6-(3,5-difluorophenyl)-6-oxohexanoate is a difluorophenyl-substituted aryl alkyl ketone bearing a terminal ethyl ester, constituting a 1,6-dicarbonyl system useful for cyclizations and chemoselective reductions.

• From Product Data

  • Product Name: Ethyl 6-(3,5-difluorophenyl)-6-oxohexanoate
  • CAS: 898752-40-4
  • CID: 24727361
  • InChIKey: 450384
  • 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 (for reference only; not specifications)

  • Suggested structural description: An ethyl ester (–CO2Et) connected via a pentamethylene spacer to an aryl ketone [–(CH2)5–CO–Ar], where Ar = 3,5-difluorophenyl.
  • Approximate molecular formula (from name parsing): C15H18F2O3 (literature/computed)
  • Approximate formula weight: ~284.30 g/mol (literature/computed)
  • Possible line representation (generic): CCOC(=O)CCCCC(=O)c1cc(F)cc(F)c1 (literature/computed)

• Structural features (general)

  • Functional groups: ethyl ester, aryl ketone (benzoyl), two aryl fluorides (meta, meta).
  • Conjugation: Ketone directly conjugated to the phenyl ring; ester carbonyl is isolated by a flexible aliphatic chain.
  • Stereochemistry: None (achiral as named; no stereocenters present).
  • 2D depiction in words: From left to right, an ethyl ester carbonyl, followed by five methylene units, terminating at a benzoyl carbonyl joined to a 3,5-difluorophenyl ring.

Synthetic Utility

• Functional group leverage

  • Ester (–CO2Et): amenable to saponification, transesterification, amidation, enolate formation, and selective reductions (DIBAL → aldehyde; LAH → primary alcohol).
  • Aryl ketone (–CO–Ar): undergoes nucleophilic additions (e.g., NaBH4 reduction), Baeyer–Villiger oxidation, oxime/hydrazone formation, and protection as ketals.
  • 1,6-Dicarbonyl topology: predisposes the substrate to intramolecular aldol condensations, enabling construction of cyclohexanone/ cyclohexenone frameworks.

• Retrosynthetic value

  • Can serve as a masked cyclohexanone precursor: deprotonation at the ester α-position followed by intramolecular aldol onto the aryl ketone generates a ring; subsequent manipulations (dehydration, hydrogenation) tailor substitution.
  • Divergent vectoring: independent elaboration at the ester terminus (amide formation, homologation) and at the aryl ketone (reduction/oxidation) offers orthogonal handles for library build-out.

• Named/related transformations (literature context)

  • Dieckmann-type and intramolecular Claisen–Aldol sequences (for ring closure).
  • Baeyer–Villiger oxidation of aryl ketones to aryl esters.
  • Curtius/Schmidt pathways after ester → acid conversion to access amines/amides.

• Selectivity considerations

  • Ketone vs ester: Ketones are generally more reactive toward hydride; choose reagent/temperature to target one group selectively.
  • Aryl fluoride positions (3,5) are relatively inert to SNAr without additional activation; focus transformations on the aliphatic and carbonyl sites.

Target Specificity

Not applicable. This product is a small-molecule building block and is not a biological macromolecule or affinity reagent. No antigen/epitope, clone, isotype, or species reactivity information applies.