4-(4-Bromo-2-fluorophenoxy)oxane - ≥95% , CAS No.1239611-29-0

CAS: 1239611-29-0 Cat. No.: B964118 Formule: C₁₁H₁₂O₂FBr Poids moléculaire: 275.11 PubChem CID: 68409179

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Spécifications et pureté

≥95%

Conditions de stockage de stockage

Room temperature

Pureté

≥95%

Noms et identifiants

• Sourires canoniques: C1COCCC1OC2=C(C=C(C=C2)Br)F
• IUPAC Name: 4-(4-bromo-2-fluorophenoxy)oxane
• InChIKey: YHRRFQOLUFCRMI-UHFFFAOYSA-N
• INCHI: 1S/C11H12BrFO2/c12-8-1-2-11(10(13)7-8)15-9-3-5-14-6-4-9/h1-2,7,9H,3-6H2
• Isomères SMILES: C1COCCC1OC2=C(C=C(C=C2)Br)F
• PubChem CID: 68409179
• Poids moléculaire: 275.11

Propriétés chimiques et physiques

• Poids moléculaire: 275.110 g/mol
• XLogP3: 3.100
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 274 Da
• Monoisotopic Mass: 274 Da
• Topological Polar Surface Area: 18.500 Ų
• Heavy Atom Count: 15
• Formal Charge: 0
• Complexity: 197.000
• 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 assay or immunoapplication protocols (WB, IHC, IF, FC) apply to this small-molecule building block.

General laboratory protocols relevant to this material (literature-based):

• Cross-coupling setup (Suzuki, example outline):
  • Combine aryl bromide (this substrate), boronic acid (1.2–1.5 equiv), base (K3PO4, 3 equiv), Pd catalyst (0.5–2 mol%), and solvent mixture (dioxane/H2O 3:1) under N2.
  • Heat at 70–90°C with stirring for 4–12 h; monitor by LC–MS/HPLC.
  • Cool, dilute with EtOAc, wash with water/brine, dry (Na2SO4), concentrate, and purify by silica gel chromatography.
• Amination setup (Buchwald–Hartwig, example outline):
  • Charge aryl bromide, amine (1.2–1.5 equiv), base (NaOtBu, 2–3 equiv), Pd precatalyst (0.5–1 mol%), and toluene in a dry vessel; degas and backfill with N2.
  • Heat to 90–110°C; monitor until consumption of starting material.
  • Work up and purify as above.
• Ether cleavage to phenol (BBr3, caution):
  • Cool dry DCM to −78°C, add BBr3 dropwise (1–3 equiv), then add the substrate solution. Stir 1–3 h at −78 to 0°C, then warm if needed.
  • Quench carefully with MeOH at 0°C, then aqueous NaHCO3; extract with DCM, dry, and purify.

These outlines are starting points only and must be optimized and validated for your specific application and safety requirements.

Biological Roles

Item-specific biological data are not provided for this product and it is sold strictly for research use.

General considerations (not product-specific):

• 4-(4-Bromo-2-fluorophenoxy)oxane is a small, halogenated aryl ether used as a synthetic building block. It is not a known metabolite, cofactor, or biopolymer component.
• Halogenated aryl ethers are commonly explored in medicinal chemistry to modulate lipophilicity, metabolic stability, and binding interactions in target molecules. The para-bromo and ortho-fluoro substituents can influence π-stacking and halogen bonding in designed ligands; however, such properties depend on the final scaffold rather than this intermediate per se.
• The oxane (tetrahydropyran) moiety is a neutral, oxygen-containing ring frequently used as a polarity and conformation modulator in bioactive compounds; in this case it is linked via an aryl–O bond and may act as a temporary protecting/solubilizing appendage during lead elaboration.

No claims are made regarding biological activity, safety in vivo, or clinical relevance. For any biological testing, appropriate risk assessments, controls, and regulatory approvals are required.

Buffer Applications

This compound is a hydrophobic aryl ether building block and is not used as a buffer component. It lacks acid/base functionality suitable for defined pKa buffering ranges.

Practical guidance:

• If handling in aqueous biological buffers (e.g., for screening), dissolution generally requires a cosolvent such as DMSO or MeCN, followed by dilution into buffer with attention to final organic percentage to avoid precipitation.
• For assays, pre-formulate concentrated DMSO stocks (e.g., 10–50 mM) and keep final DMSO below assay tolerance (often ≤1–2%). Filter solutions to remove particulates.

For buffer selection itself, refer to standard buffering agents (phosphate, HEPES, MOPS, Tris), as this product does not provide buffering capacity.

Green Alternatives

While 4-(4-bromo-2-fluorophenoxy)oxane is a target substrate rather than a process solvent, greener choices can be made for its synthesis and downstream transformations.

• Greener solvent options (literature guidance):

  • Replace THF with 2-MeTHF or CPME for many Pd-catalyzed couplings; both offer improved stability toward peroxidation and enable phase separations.
  • Use ethanol/water or propylene carbonate where feasible for Suzuki couplings, leveraging aqueous bases.
  • Employ micellar catalysis (e.g., TPGS-750-M in water) to reduce organic solvent consumption during cross-couplings, with in-flask extraction for isolation.

• Catalyst and base considerations:

  • Modern high-activity Pd catalysts (e.g., precatalysts with bulky biaryl phosphines) function at ppm levels, minimizing precious metal usage and facilitating easier metal removal.
  • Avoid stoichiometric tin or zinc reagents when possible; prefer boron-based couplings (Suzuki) for better EHS profiles.

• Energy and waste minimization:

  • Conduct reactions at ambient temperature when possible using more active catalysts.
  • Employ continuous flow for exotherm control and reduced solvent volumes during halogenation or O-arylation steps.

Small comparison (general):

• Traditional: THF/dioxane, Stille coupling, chlorinated workups.
• Greener: 2-MeTHF/EtOH–water, Suzuki coupling, aqueous micellar media, and non-chlorinated extraction (EtOAc/heptane).

Trade-offs: greener solvents may alter solubility and rate; re-optimization of base, ligand, and temperature is often required to maintain yields.

Pharmaceutical Uses

Item-specific pharmacopeial status or excipient roles: Not specified for this item; refer to CoA/Spec Sheet.

General context (not product-specific, no therapeutic claims):

• 4-(4-Bromo-2-fluorophenoxy)oxane is best classified as a synthetic intermediate/building block. Such aryl halides are frequently incorporated into medicinal chemistry programs to access analog libraries through cross-coupling or nucleophilic substitution.
• Potential roles in pharmaceutical R&D workflows:
  • Intermediate en route to candidate APIs by para diversification (Suzuki/Buchwald) while retaining ortho-fluoro as a handle or as a metabolic stabilizer.
  • Scaffold for SAR exploration where the oxane moiety modulates polarity and solubility of leads.
• Manufacturing considerations:
  • Residual palladium from cross-couplings downstream may necessitate metal scavenging; the aryl–O–oxane functionality can interact with scavengers—screen silica-bound thiols, mercaptans, or dithiocarbamates.
  • Control of halogen content and potential hydrolytic byproducts (phenol) is important for regulatory impurity profiling.

No claims are made for direct therapeutic or excipient use. Any application toward drug substance manufacture must comply with GMP and ICH guidelines, with full impurity and residual solvent profiling.

Physical Properties

Item-specific specifications (this product):

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

General/literature expectations for compounds of this class (aryl–alkyl ethers, halogenated phenoxy–oxane; non-binding):

• Formula and mass (computed from name): C11H12BrFO2; ~275.12 g/mol.
• Physical state: small aryl ethers of this size may be low-melting solids or viscous liquids; exact melting/boiling points for this CAS are not located here and should be confirmed from primary data.
• Density, refractive index, UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility profile (qualitative, literature-based): typically sparingly soluble in water; soluble in common organics such as dichloromethane, chloroform, ethyl acetate, THF, toluene, and acetonitrile; actual solubility should be experimentally verified.
• LogP (qualitative): halogenated aryl ethers generally exhibit moderate to high hydrophobicity; an elevated logP relative to non-halogenated analogs is expected; verify experimentally if needed.

Notes for practitioners:

• If crystallinity is required for purification, consider slow evaporation from hexanes/EtOAc or heptane/toluene blends; confirm solvates.
• Determine exact thermal behavior (DSC/TGA) prior to scale-up to define safe heating ranges and potential decomposition onset.
• For analytical QC, GC may be feasible if volatility permits; otherwise use HPLC/UPLC with PDA/ELSD and HRMS.

Quality and Grades

Item-specific quality information:

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

Guidance for interpreting grades (general, not item-specific):

• Research/technical grade is typically suitable for synthetic transformations and method development. If trace metal content, residual solvents, or low UV background are critical (e.g., for photophysical studies or LC impurity thresholds), request an analytical reagent (AR) or HPLC grade material and consult the CoA for actual impurity limits.
• Halogenated aryl building blocks destined for cross-coupling benefit from tight control of halide content and minimal phenolic impurities. Residual phenol or hydrolysis products can poison catalysts; review GC/HPLC area% and water content on the CoA.
• UV absorbance: if using for photochemical or analytical applications, low-UV or spectroscopy grades reduce baseline noise; verify specific UV cutoff on the CoA when relevant.

Batch-specific recommendations:

• Request CoA data for identity (1H/13C NMR, HRMS), purity (HPLC/GC area%), residual solvents, water (Karl Fischer), and halide assay.
• If sensitive catalysis is planned (e.g., ppm-level Pd couplings), consider prewashing over basic alumina or recrystallization to remove adventitious acids/phenols; document any additional internal QC.

Reaction and Applications

As a bifunctional aryl ether featuring para-bromide and ortho-fluoride on the phenyl ring, 4-(4-bromo-2-fluorophenoxy)oxane is a versatile building block for stepwise diversification.

• Cross-coupling at aryl bromide (literature practice):
  • Suzuki–Miyaura coupling with aryl/alkenyl boron reagents to install diverse aryl groups para to the phenoxy linkage. Pd(0) or Pd(II) precatalysts with phosphine or NHC ligands are typical. The ortho-F often survives Suzuki conditions, enabling two-point diversification.
  • Buchwald–Hartwig amination to introduce anilines at the para position; ligand-controlled selectivity avoids C–O cleavage. Base choice (NaOtBu, Cs2CO3) and solvent (toluene, dioxane, 2-MeTHF) are tuned for substrate solubility.
  • Stille/Negishi/Kumada couplings are alternative manifolds when compatible partners are available.
• Chemoselectivity considerations:
  • C–Br is typically more reactive than C–F in oxidative addition; thus para functionalization proceeds first, leaving the ortho-F intact for subsequent transformations.
  • The aryl–O–oxane bond is generally stable under Pd-catalyzed couplings but can be cleaved by strong Lewis acids (e.g., BBr3) to unmask the phenol if desired.
• Transformations at the aryl fluoride:
  • SNAr at C–F generally requires strong electron-withdrawing activation ortho/para to the leaving group; the phenoxy substituent is electron-donating, so classic SNAr is disfavored. However, metal-catalyzed defluorinative functionalizations (e.g., Ni- or Cu-mediated) or directed lithiation followed by quench can be explored with appropriate precautions.
• Manipulation of the oxane moiety:
  • The oxane-bound alkyl ether can undergo selective cleavage to reveal the phenol (BBr3, BCl3) or, under acidic conditions, potential rearrangements/cleavage of the tetrahydropyranyl portion.

Applications: library synthesis, SAR exploration in medicinal chemistry, materials motifs where halogenated aryl ethers impart hydrophobicity and electronic tuning.

Reaction Conditions

General literature conditions for representative transformations of aryl bromides bearing phenoxy substituents (guidance only; optimize for your system):

• Suzuki–Miyaura coupling (C–Br → C–C):

  • Catalyst: Pd(PPh3)4 (1–3 mol%) or Pd-precatalyst (e.g., XPhos/Pd G3 0.5–1 mol%).
  • Base: K2CO3, K3PO4, or Cs2CO3 (2–3 equiv) in H2O or aq. solvent.
  • Solvent: 1,4-dioxane/H2O (3:1), THF/H2O, 2-MeTHF/H2O, or EtOH/H2O.
  • Temperature/time: 50–90°C, 2–16 h. Or room temperature with highly active catalysts.
  • Notes: Ortho-F typically remains intact; avoid strong acids that could cleave the aryl–O bond.

• Buchwald–Hartwig amination (C–Br → C–N):

  • Catalyst/ligand: Pd2(dba)3 (1 mol% Pd) with BrettPhos or RuPhos (2–4 mol%), or precatalyst (e.g., BrettPhos Pd G3, 0.5–1 mol%).
  • Base: NaOtBu or Cs2CO3 (2–3 equiv).
  • Solvent: toluene, 1,4-dioxane, or 2-MeTHF.
  • Temperature: 60–110°C.
  • Notes: Electron-rich aryl ethers often couple smoothly; minimize protic impurities.

• Aryl–O bond cleavage to unveil phenol:

  • Reagent: BBr3 (1–3 equiv per aryl–O bond) in dry DCM at −78 to 0°C then warm to rt.
  • Time: 1–12 h depending on substrate.
  • Quench: MeOH or aqueous NaHCO3 cautiously; control exotherm.

• Defluorinative functionalization (advanced, substrate-dependent):

  • Ni-catalyzed cross-coupling under reducing conditions (e.g., NiCl2(dppp), Zn) can activate aryl–F in specific contexts; extensive optimization required.

All parameters above are literature-style starting points; run small-scale screens to identify optimal ligand/base/solvent combinations for this specific substrate.

Safety and Handling

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 considerations for halogenated aryl ethers (literature/practice guidance; not product-specific):

• Likely hazards: combustible liquid/solid; may cause skin/eye irritation and respiratory irritation if aerosols or vapors are generated during handling; avoid prolonged exposure.
• Peroxide formation: aryl–alkyl ethers are significantly less prone to peroxide formation than dialkyl ethers, but long-term storage in air/light may lead to slow oxidation; periodic peroxide testing is prudent when distillation is contemplated.
• Incompatibilities: strong oxidizers (risk of exotherm), strong Lewis acids/halophiles (e.g., BBr3, AlCl3) which can cleave aryl–O bonds; strong bases at elevated temperature may induce elimination/side reactions.
• Personal protective equipment: lab coat, safety glasses or splash goggles, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a fume hood to control vapors and dust/aerosols.
• First-aid overview: eye—rinse cautiously with water for several minutes; skin—wash with soap and water and remove contaminated clothing; inhalation—move to fresh air; ingestion—rinse mouth and seek medical attention. Always follow institutional SOPs.
• Fire safety: use CO2, dry chemical, or foam. Water spray for cooling containers.
• Spill response: contain with inert absorbent (vermiculite, sand), collect for disposal. Prevent entry into drains.

Always consult the product-specific SDS for authoritative hazard classification, exposure limits, and emergency measures.

Solvent Selection

This product is a halogenated aryl ether building block rather than a process solvent. Solvent discussion here focuses on dissolving and reacting it efficiently.

• Polarity and solubility (general): aryl–alkyl ethers with Br/F substituents are typically nonpolar to moderately polar and dissolve well in chlorinated solvents (DCM, CHCl3), ethers (THF, 2-MeTHF, MTBE), aromatics (toluene), and polar aprotics (DMF, DMAc, NMP, MeCN). Water solubility is usually very low.
• For cross-coupling at the aryl bromide:
  • Ethanol/water, dioxane/water, THF/water, or toluene/EtOH mixtures are commonly used, often with aqueous base. Choice depends on catalyst/ligand system and substrate solubility.
  • For green process development, 2-MeTHF or CPME can replace THF/MTBE; micellar media (TPGS-750-M in water) can be effective for some Pd-catalyzed couplings.
• For nucleophilic substitutions on the oxane side (e.g., ether cleavage or exchange): polar aprotics (DCM with BBr3, or TFA/DCM blends; alternatively DMF/DMSO for base-mediated transformations) are typical.
• Crystallization and workup:
  • Nonpolar antisolvents (hexanes/heptane) can induce crystallization from EtOAc or toluene. If oiling-out occurs, use MeOH/MTBE or EtOAc/hexanes solvent pairs.
  • For extractions, DCM or EtOAc provide efficient partitioning from aqueous phases containing inorganic salts and bases.

Always confirm solubility and stability in the chosen medium on small scale prior to scale-up.

Storage and Reconstitution

Item-specific instructions 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.

General handling and storage recommendations (not item-specific):

• Store tightly closed in a dry, inert atmosphere (desiccator or with desiccant in the container). Protect from prolonged exposure to air and light to minimize potential oxidative degradation.
• If long-term storage is anticipated, consider storing under nitrogen/argon and in amber glass.
• Avoid contact with strong acids, strong Lewis acids (which can cleave aryl–O bonds), and strong oxidizers.
• For solution storage (e.g., analytical standards): prepare stock solutions in anhydrous solvents such as DMSO, THF, or MeCN at appropriate concentrations; store at 2–8°C or −20°C depending on solvent stability, in sealed vials. Validate stability by LC over time.
• Freeze–thaw: if storing solutions frozen, aliquot to avoid repeated freeze–thaw cycles that may introduce moisture and degrade quality.

Research use note: For research use only. Consult the SDS and CoA for lot-specific guidance on stability, impurities, and any additional storage precautions.

Structure and Identity

Brief description: 4-(4-Bromo-2-fluorophenoxy)oxane is an aryl–alkyl ether comprising a tetrahydropyran (oxane) ring bearing a para-bromo, ortho-fluoro phenoxy substituent at the 4-position.

• Item-specific identifiers (from Product Data)

  • SKU: B964118
  • Product Name: 4-(4-Bromo-2-fluorophenoxy)oxane
  • CAS: 1239611-29-0
  • PubChem CID: 68409179
  • InChIKey: 437597 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Computed/literature structural information (non-item-specific)

  • Core scaffold: tetrahydropyran (oxane) ring (six-membered, one ring oxygen) substituted at C-4 by an O–aryl group.
  • Functional groups: aryl–alkyl ether (Ar–O–R), cyclic acetal ether (oxane), aryl bromide (para), aryl fluoride (ortho).
  • Stereochemistry: none expected at the aryl moiety; the oxane ring is achiral overall in the absence of additional stereogenic centers.
  • 2D description in words: a six-membered saturated ring with one oxygen (oxane). At the carbon opposite the ring oxygen (position 4), an oxygen substituent connects to a monosubstituted phenyl ring bearing bromine at the para position and fluorine at the ortho position relative to the ether linkage.

• Formula and formula mass (literature calculation, for reference only)

  • Molecular formula (computed): C11H12BrFO2
  • Formula weight (computed): ~275.12 g/mol

Note: Use the Certificate of Analysis/SDS for authoritative structural identifiers for this specific lot.

Synthetic Utility

Key reactive elements and strategic value (literature-based, general guidance):

• Aryl bromide (para): excellent handle for Pd-catalyzed C–C and C–N bond formation. Selective activation of C–Br over C–F enables orthogonal, sequential diversification.
• Aryl fluoride (ortho): robust handle that resists many conditions; can be leveraged for late-stage defluorinative functionalization (Ni, Cu) or directed ortho metalation strategies leveraging the phenoxy oxygen as a directing group.
• Aryl–O–oxane ether: stable under many cross-coupling conditions; can be cleaved with Lewis acids (BBr3, AlCl3) to reveal the phenol, enabling further derivatization (sulfonylation, etherification, O-arylation).

Retrosynthetic perspectives:

• Forward synthesis often arises from nucleophilic substitution of a 4-bromo-2-fluorophenoxide anion onto a 4-halo- or 4-tosyloxytetrahydropyran, or via Mitsunobu coupling of 4-bromo-2-fluorophenol with 4-hydroxytetrahydropyran.
• Orthogonal functionalization: first, Pd-catalyzed coupling at C–Br; second, optional manipulation at C–F or phenoxy cleavage to unmask phenol; third, installation of alternate groups (e.g., sulfonates, carbamates) on the phenolic oxygen after deprotection.

Analytical/handling tips:

• Monitor cross-couplings by LC–MS; the mass shift relative to the aryl bromide is diagnostic as Br is lost during coupling.
• Verify integrity of the aryl–O linkage post-reaction by 19F NMR (retention of the ortho-F signal) and 1H/13C NMR (oxane signals at ~3.4–4.0 ppm for O-CH, literature ranges).

Target Specificity

This product is a small-molecule chemical building block and is not an affinity reagent or biological targeting agent. Consequently, there is no antigen/epitope specificity, isotype, or species reactivity associated with it.

• Item-specific antibody/bioreagent fields: Not applicable.
• For users seeking target-specific reagents (e.g., antibodies, ligands), please refer to the appropriate catalog sections. This compound is intended for synthetic chemistry applications.

Foire aux questions

What is the purity of this product?

This product is supplied at ≥95% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.

How should this product be stored?

Store at room temperature.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 1239611-29-0, the molecular formula is C11H12O2FBr, and the molecular weight is 275.11 g/mol. InChIKey YHRRFQOLUFCRMI-UHFFFAOYSA-N.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.