Methyl 2-(3-bromo-5-fluorophenyl)acetate - ≥98% , CAS No.937732-38-2

CAS: 937732-38-2 Cat. No.: M1028544 Formula: C₉H₈BrFO₂ Peso molecolare: 247.060

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

Specifiche e purezza

≥98%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥98%

Nomi e identificatori

Sorrisi canonici

COC(=O)CC1=CC(=CC(=C1)Br)F

IUPAC Name

methyl 2-(3-bromo-5-fluorophenyl)acetate

InChIKey

AJSCFDHWZUZCNE-UHFFFAOYSA-N

INCHI

1S/C9H8BrFO2/c1-13-9(12)4-6-2-7(10)5-8(11)3-6/h2-3,5H,4H2,1H3

Peso molecolare

247.060

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Classe Benzene and substituted derivatives
      • Subclass Halobenzenes

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Halobenzenes
• Intermediate Tree Nodes: Not available
• Direct Parent: Fluorobenzenes
• Alternative Parents: Bromobenzenes Aryl fluorides Aryl bromides Methyl esters Monocarboxylic acids and derivatives Organofluorides Organobromides Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Bromobenzene - Fluorobenzene - Aryl bromide - Aryl fluoride - Aryl halide - Methyl ester - Carboxylic acid ester - Carboxylic acid derivative - Monocarboxylic acid or derivatives - Organobromide - Organofluoride - Carbonyl group - Organooxygen compound - Hydrocarbon derivative - Organic oxide - Organic oxygen compound - Organohalogen compound - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as fluorobenzenes. These are compounds containing one or more fluorine atoms attached to a benzene ring.
• 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: 247.060 g/mol
• XLogP3: 2.500
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 3
• Exact Mass: 245.969 Da
• Monoisotopic Mass: 245.969 Da
• Topological Polar Surface Area: 26.300 Ų
• Heavy Atom Count: 13
• Formal Charge: 0
• Complexity: 186.000
• 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 biological assay protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule building block in the Product Data. For synthetic applications, see the Reaction Conditions and Synthetic Utility sections for literature-based procedural guidance.

Biological Roles

This product is a synthetic organic building block rather than a biomolecule. It does not have established endogenous biological roles.

General context (literature):

• Arylacetic acid derivatives are found in diverse bioactive scaffolds; however, the presence of a benzylic ester and aryl bromide/fluoride in this compound signifies it is intended for chemical synthesis rather than as a biological probe.
• The ester can be hydrolyzed to the corresponding acid or converted to amides often encountered in medicinal chemistry libraries, but any bioactivity would be emergent from the final structures synthesized rather than from this intermediate itself.

Use strictly for research and laboratory synthesis. No medical, diagnostic, or clinical applications are implied or supported for this catalog item.

Buffer Applications

Not typically applicable. Methyl 2-(3-bromo-5-fluorophenyl)acetate is a hydrophobic organic building block and is not used as a buffering agent. For aqueous work, buffers may be used to control pH during hydrolysis or coupling reactions, but this compound itself does not form a buffering system. Refer to Reaction & Applications and Reaction Conditions for more relevant guidance.

Green Alternatives

While the compound itself is a substrate, greener choices can be made for solvents, bases, and catalysts in its transformations. Below are literature-based options and tradeoffs.

Greener solvent swaps (literature suggestions):

• Replace THF with 2-MeTHF for cross-couplings and reductions: renewable origin, better phase separation; similar polarity. Tradeoff: slightly higher boiling point.
• Replace 1,4-dioxane with CPME or 2-MeTHF: lower toxicity and peroxide propensity than dioxane. Tradeoff: may require condition re-optimization.
• Use EtOAc or Me-THF instead of DCM for extractions/workups when feasible; avoid halogenated waste.

Base and reagent considerations:

• Prefer K3PO4 or K2CO3 in water/biobased solvent mixtures for Suzuki reactions over harsher bases. Aqueous micellar catalysis (e.g., TPGS-750-M) can reduce organic solvent usage.
• For reductions, consider catalytic hydrogenation (Raney Ni, Pd/C) where chemoselectivity allows, instead of stoichiometric hydrides.

Catalyst choices:

• Employ ligand-optimized Pd systems that operate at low loadings (≤0.5 mol%) or Ni-based catalysts for Ar–Br couplings to reduce precious metal consumption.

Energy footprint:

• Microwave or flow chemistry can reduce reaction times/energy use; flow also improves heat/mass transfer for exothermic steps (e.g., borylation, amination).

Waste minimization:

• Design telescoped sequences: e.g., borylation–Suzuki without isolation of the boronate. Use carbonate bases to enable simple aqueous workups.

Note: Effectiveness is substrate- and transformation-dependent; verify by small-scale screens.

Pharmaceutical Uses

Formulation/excipient role: Not applicable. This compound is not used as a pharmaceutical excipient.

Relevance to pharmaceutical R&D (general, non-therapeutic):

• Serves as a synthetic intermediate in medicinal chemistry for constructing halogenated arylacetic acid derivatives, amides, and related scaffolds.
• Orthogonal handles (Ar–Br for cross-coupling; benzylic α-position for diversification) facilitate rapid generation of analog libraries during hit-to-lead and lead optimization.
• The ester can be hydrolyzed to the free acid for convergent amide couplings; protecting-group strategy may leverage the methyl ester’s stability to many conditions.

Regulatory status: No pharmacopeial monograph is implied. Any use in GMP or clinical manufacturing would require independent qualification and specification setting.

Note: This product is supplied strictly for research use only, not for human or veterinary use.

Physical Properties

Item-specific specs (from Product Data):

• 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.

Computed/literature values and expectations (for the structure C9H8BrFO2; informational only):

• Molecular formula (computed): C9H8BrFO2
• Molecular weight (computed): ~247.06 g/mol
• Physical state: Aromatic methyl esters of comparable substitution are often low-melting solids or high-boiling liquids; the exact state depends on lot-specific purity and packing and is not specified here.
• Solubility (general): Expected to be soluble in common organic solvents (DCM, EtOAc, THF, toluene, acetonitrile) and sparingly soluble in water due to the hydrophobic aryl core.
• Volatility: Low to moderate; anticipate a boiling point well above ambient, enabling standard handling on the bench.
• Partitioning: The aryl ester with one Br and one F generally exhibits moderate to high logP; facilitates extraction from aqueous workups into organic phases.
• Spectroscopic features: Ester carbonyl IR ~1735 cm−1 (literature); 1H NMR with benzylic CH2 singlet ~3.5–3.7 ppm and OMe singlet ~3.6–3.8 ppm; aromatic region 6.8–7.8 ppm (solvent-dependent). 19F NMR: a single aryl F resonance typically between −110 to −130 ppm (literature). These are general expectations, not item-specific specs.

For exact BP/MP, density, refractive index, and UV cutoff for this catalog item, consult the CoA/Spec Sheet.

Quality and Grades

Item-specific (from Product Data):

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

Guidance on grades and implications (general):

• Research-grade halogenated building blocks are typically supplied with assay by NMR/GC/LC and controlled residual solvents. Where specified, HPLC grade refers to low UV background and minimal non-volatile residues—more relevant for solvents rather than solids.
• For coupling building blocks, low levels of protic/halide impurities and peroxides are important for reproducibility. If a stabilizer is present (e.g., acid inhibitor), it will be declared on the CoA; absence of a declaration generally implies no intentional stabilizer.
• Trace metal content, water content, and residual halide are critical for Pd-catalyzed reactions. If your process is sensitive, request or check the Spec Sheet for Karl Fischer, ICP-MS/ICP-OES, and residual solvent data.
• Lot-to-lot consistency: Check CoA for melting range (if solid), GC purity, and NMR identity confirmation. For air/moisture-sensitive analogs, packaging under inert gas may be provided; if applicable it will be listed on the label/CoA.

Recommendation: Align your grade requirements with the intended use (e.g., medicinal chemistry vs. process screening). For this catalog item, exact purity, residual solvent, and metal limits are Not specified for this item; refer to CoA/Spec Sheet.

Reaction and Applications

Functional handles and typical uses (literature):

• Aryl bromide (Ar–Br): robust handle for Pd-catalyzed cross-couplings (Suzuki–Miyaura to install aryl/alkenyl/heteroaryl; Sonogashira to append alkynes; Heck arylation of alkenes; Buchwald–Hartwig amination to introduce anilines/anilides). Miyaura borylation (B2pin2) affords the corresponding boronate ester for further diversification.
• Benzylic methylene α to ester: enolizable position supports alkylation (e.g., LDA, NaHMDS), Knoevenagel and related condensations, and halogenation (NBS for benzylic bromination) followed by substitution.
• Ester group: hydrolysis to the acid (for amide coupling), reduction to alcohol (DIBAL-H for aldehyde at −78 °C; LiAlH4/NaBH4 variants for alcohol), or transesterification to tune protecting group.
• Aryl fluoride: less reactive in cross-coupling, but can engage in SNAr when activated by strong electron-withdrawing groups or under metalation/halogen–lithium exchange with careful cryogenic control.

Application domains (general, non-clinical):

• Medicinal chemistry: halogenated arylacetic acids/esters are common cores for SAR campaigns; orthogonal handles (Ar–Br, benzylic α-position) enable rapid library synthesis.
• Materials/functional molecules: introduction of fluoro/bromo motifs tunes lipophilicity and electronic character in OLED/OPV small molecules and ligands.
• Isotopic/label variants: the ester/benzylic site facilitates introduction of labels (e.g., 13C at carbonyl, deuteration at benzylic position) using established methods.

Practical tips:

• Degas solvents and use dry glassware for cross-couplings. Trace water can be beneficial with aqueous bases but avoid wet DMF/MeCN for air-sensitive catalysts.
• For α-alkylations, pre-form the lithium enolate at −78 °C in THF; quench carefully to avoid over-alkylation or Claisen-type side reactions.
• Monitor by LC–MS or GC–MS; aryl bromide often shows characteristic isotope pattern (M and M+2).

Reaction Conditions

All conditions below are literature-general guidance for aryl bromide methyl arylacetates; optimize for your system.

• Suzuki–Miyaura coupling (Ar–Br):
  • Catalyst: Pd(PPh3)4 (1–2 mol%) or Pd(dppf)Cl2·DCM (1 mol%).
  • Base: K2CO3 or K3PO4 (2–3 equiv).
  • Solvent: 1,4-dioxane/H2O (3:1), THF/H2O, or toluene/H2O.
  • Temperature/time: 70–100 °C, 2–16 h. Typical isolated yields: 60–90% depending on partners.
• Buchwald–Hartwig amination:
  • Catalyst/ligand: Pd2(dba)3 (1 mol% Pd) with XPhos/BrettPhos-type ligands.
  • Base: NaOtBu or Cs2CO3.
  • Solvent: Toluene, dioxane, or t-AmylOH.
  • 80–110 °C, 6–20 h.
• Sonogashira coupling:
  • Catalyst: Pd(PPh3)2Cl2 (1–2 mol%) with CuI (2–5 mol%) or copper-free systems.
  • Base: Et3N, DIPEA, or i-Pr2NH.
  • Solvent: THF, DMF, or MeCN; 25–80 °C.
• Miyaura borylation:
  • Reagents: B2pin2 (1.2–1.5 equiv), Pd(dppf)Cl2 (1–2 mol%), KOAc (3 equiv).
  • Solvent: DMSO, dioxane, or DMF; 70–90 °C, 4–12 h.
• Benzylic α-alkylation:
  • Base: LDA (1.1–1.5 equiv) generated in situ from n-BuLi/diisopropylamine at −78 °C.
  • Solvent: Anhydrous THF.
  • Electrophile: Alkyl halide added slowly at −78 to −20 °C; warm to 0–25 °C.
• Ester hydrolysis (saponification):
  • Base: NaOH or KOH (1–3 equiv).
  • Solvent: MeOH/H2O/THF; rt to reflux, 1–6 h; followed by acidification.
• Reductions:
  • DIBAL-H (1.1–1.5 equiv) in toluene/hexanes at −78 °C to aldehyde; quench carefully.
  • LiAlH4 in THF at 0–25 °C to alcohol.

Note: Monitor for potential debromination or transesterification under harsh/basic conditions. Control water content to maintain catalyst activity in couplings.

Safety and Handling

GHS classification (from Product Data):

• Signal word: Not specified for this item; refer to SDS.
• Hazard statements (H-Statements): Not specified for this item; refer to SDS.
• GHS classification/pictograms: Not specified for this item; refer to SDS.

General laboratory safety guidance (informational; defer to SDS for authoritative details):

• Likely hazards: As an aryl ester/halogenated organic, may cause skin/eye irritation and may be harmful if swallowed, inhaled, or absorbed. Avoid aerosol formation.
• PPE: Use chemical-resistant gloves (e.g., nitrile), safety goggles/face protection, lab coat. Handle in a fume hood to avoid inhalation of vapors or dust.
• Handling: Avoid heat, sparks, and open flame. Prevent contact with strong bases during storage and with strong oxidizers. In reactions, add bases and nucleophiles slowly with cooling if needed due to exotherms.
• Incompatibilities: Strong oxidizing agents; strong nucleophiles/bases can saponify the ester. Organolithiums/alkoxides can deprotonate the benzylic position.
• First aid overview: If on skin/eyes, rinse cautiously with water for several minutes; remove contaminated clothing. If inhaled, move to fresh air. If ingested, rinse mouth; do not induce vomiting; seek medical attention. Always follow site SOPs.
• Spill and disposal: Absorb small spills with inert material; collect for disposal according to local regulations. Avoid release to the environment; halogenated organics may require specialized waste streams.

Always consult the product SDS for this specific item and lot before use.

Solvent Selection

Relevance: This product is an organic building block, not a solvent. The following guidance focuses on selecting solvents to dissolve and react with this compound effectively.

General solubility/miscibility profile (literature expectations):

• Good solubility: DCM, chloroform, THF, 1,4-dioxane, acetonitrile, toluene, ethyl acetate, DMF, DMSO.
• Limited solubility: Water and highly polar protic media without co-solvent.

Choosing solvents by application:

• Pd-catalyzed cross-couplings (Ar–Br): 1,4-dioxane/H2O, THF/H2O, toluene, or MeCN are common. Aqueous base (K2CO3, K3PO4, Na2CO3) pairs well with dioxane or THF; stronger bases (Cs2CO3) tolerate MeCN or toluene.
• Benzylic α-functionalization: Anhydrous THF or MTBE for LDA-mediated alkylation (−78 to 0 °C); DMF/DMSO for phase-transfer/alkyl halide substitutions at milder temperatures.
• Hydrolysis to the acid: MeOH/H2O/THF with NaOH or KOH; use co-solvent to maintain solubility.
• Reductions (to alcohol or aldehyde): THF, Et2O, or DCM with hydride reagents; control temperature to manage exotherms.

Small comparison (literature):

• THF vs 2-MeTHF: similar polarity; 2-MeTHF improves phase separation and is often more sustainable.
• Dioxane vs CPME: CPME offers broader stability range and lower peroxide tendency.

Tip: Start with 10–30 mg/mL screening solutions in DCM, THF, or MeCN for reaction scouting. Adjust solvent polarity to balance substrate and reagent solubility.

Storage and Reconstitution

Item-specific (from Product Data):

• Recommended storage: Room temperature.

General storage guidance for this compound class:

• Store tightly closed in a dry, well-ventilated place. Protect from moisture and prolonged light exposure.
• If long-term storage is anticipated, consider amber glass and a desiccant. For highly air/moisture-sensitive processes, subdivide into small aliquots under inert gas to minimize headspace oxygen/water pickup during repeated openings.
• Incompatibilities in storage: Avoid contact with strong oxidizers and strong bases that could saponify the ester.

Reconstitution/solubilization:

• Supplied as a neat material (solid or liquid not specified). No reconstitution is required. To prepare stock solutions for screening, dissolve in anhydrous DCM, THF, MeCN, DMF, or DMSO at the desired concentration (e.g., 10–100 mg/mL). Filter if particulate is present.

Shipping:

• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

Stability notes:

• Ester functionality is generally stable under neutral, dry conditions. Avoid extended exposure to strong bases or acids if not intended. Always refer to the CoA/SDS for any lot-specific stability advisories.

Structure and Identity

Brief description: Methyl 2-(3-bromo-5-fluorophenyl)acetate is an arylacetic acid methyl ester bearing a bromine and a fluorine substituent on the aromatic ring. It is a halogenated building block useful for cross-coupling and side-chain functionalization.

Item-specific (from Product Data):

• Product name: Methyl 2-(3-bromo-5-fluorophenyl)acetate (SKU: M1028544)
• CAS: 937732-38-2
• InChIKey: 7322 (as provided)
• Storage: Room temperature
• Research use: For research use only

Computed/literature identity (structure-derived; not item-specific specs):

• Molecular formula (computed from name): C9H8BrFO2
• Molecular weight (computed): ~247.06 g/mol
• Canonical SMILES (computed): COC(=O)Cc1cc(Br)cc(F)c1
• Key functional groups: methyl ester (–CO2Me), benzylic methylene (–CH2–), aryl bromide (Ar–Br), aryl fluoride (Ar–F)
• Structural description (2D): a phenyl ring substituted at the benzylic 1-position by –CH2–CO2Me; ring additionally bears Br at the meta (3-) position and F at the meta’ (5-) position relative to the benzylic substituent. No stereocenters; achiral.

General notes:

• The Ar–Br bond offers a versatile handle for Pd-catalyzed cross-couplings (Suzuki–Miyaura, Buchwald–Hartwig, Sonogashira).
• The benzylic methylene α to the ester is enolizable and amenable to base-mediated alkylation or condensation chemistry.
• The aryl fluoride is less reactive in cross-coupling but can participate in directed metalation or SNAr under activating conditions.

Refer to the CoA/Spec Sheet for definitive identity confirmations (NMR, GC/LC purity, and exact identifiers) for this specific lot.

Synthetic Utility

Reactive elements and strategies (literature):

• Aryl bromide vector: Entry to C–C and C–N bond formation via Pd- or Ni-catalyzed cross-couplings. Examples:
  • Suzuki–Miyaura: install aryl/heteroaryl/alkenyl partners using boronic acids/esters.
  • Buchwald–Hartwig amination: form anilines/anilides with amines under ligand-enabled conditions.
  • Sonogashira: append terminal alkynes (with or without copper co-catalyst).
  • Miyaura borylation: generate aryl–Bpin intermediates for two-step diversification.
• Benzylic α-position (adjacent to the ester):
  • Alkylation using LDA/NaHMDS to form lithium/sodium enolates; electrophiles include alkyl halides, aldehydes (aldol-type), and Michael acceptors.
  • Halogenation (NBS, NCS) to benzylic halides, enabling subsequent SN2 displacement with N/O/S nucleophiles.
• Ester transformations:
  • Hydrolysis (NaOH/KOH, MeOH/H2O) to acid; acid chlorides (SOCl2, (COCl)2) for amide formation.
  • Reductions: DIBAL-H to aldehyde at −78 °C; LiAlH4 to benzyl alcohol; catalytic hydrogenation if compatible.
  • Transesterification to alter protecting group (acidic/basic catalysis).
• Aryl fluoride: Typically inert under standard cross-coupling; can participate in SNAr if the ring is further activated or under directed ortho-metalation protocols.

Retrosynthetic value:

• Decouples diversification along two orthogonal axes: aryl substitution (via Ar–Br) and side-chain elaboration (via α-chemistry and ester interconversions), enabling efficient parallel synthesis.

Purification notes:

• Halogenated aromatics often purify well by column chromatography on silica; consider hexanes/EtOAc or toluene/EtOAc gradients; monitor for tailing due to polar byproducts.

Target Specificity

Not applicable. This product is a small-molecule building block and does not possess biological target specificity (no antigen, epitope, or isotype information). No antibody or protein-binding characteristics are provided in the Product Data.