Ethyl 5-bromo-2-ethoxynicotinate - ≥97% , CAS No.1310416-59-1

CAS: 1310416-59-1 Cat. No.: E1034736 Formula: C₁₀H₁₂BrNO₃ Peso molecolare: 274.12 PubChem CID: 74889502

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

Specifiche e purezza

≥97%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥97%

Nomi e identificatori

• Sorrisi canonici: CCOC1=C(C=C(C=N1)Br)C(=O)OCC
• IUPAC Name: ethyl 5-bromo-2-ethoxypyridine-3-carboxylate
• InChIKey: WTBGNLKERTVJQR-UHFFFAOYSA-N
• INCHI: 1S/C10H12BrNO3/c1-3-14-9-8(10(13)15-4-2)5-7(11)6-12-9/h5-6H,3-4H2,1-2H3
• Isomeri SMILES: CCOC1=C(C=C(C=N1)Br)C(=O)OCC
• PubChem CID: 74889502
• Peso molecolare: 274.12

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Classe Pyridines and derivatives
      • Subclass Pyridinecarboxylic acids and derivatives

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Pyridines and derivatives
• Subclass: Pyridinecarboxylic acids and derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Pyridinecarboxylic acids
• Alternative Parents: Alkyl aryl ethers Aryl bromides Heteroaromatic compounds Carboxylic acid esters Azacyclic compounds Organonitrogen compounds Organobromides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Pyridine carboxylic acid - Alkyl aryl ether - Aryl bromide - Aryl halide - Heteroaromatic compound - Carboxylic acid ester - Carboxylic acid derivative - Ether - Azacycle - Organobromide - Organohalogen compound - Hydrocarbon derivative - Organic nitrogen compound - Organic oxide - Organonitrogen compound - Organooxygen compound - Organic oxygen compound - Aromatic heteromonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as pyridinecarboxylic acids. These are compounds containing a pyridine ring bearing a carboxylic acid 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

Proprietà chimiche e fisiche

• Peso molecolare: 274.110 g/mol
• XLogP3: 2.400
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 5
• Exact Mass: 273 Da
• Monoisotopic Mass: 273 Da
• Topological Polar Surface Area: 48.400 Ų
• Heavy Atom Count: 15
• Formal Charge: 0
• Complexity: 213.000
• 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 tested biological assay protocols (e.g., WB, IHC, IF, FC) are provided for this small-molecule building block. For chemical applications, refer to the Reaction Conditions, Synthetic Utility, and Reaction & Applications sections for general experimental guidance.

Biological Roles

• Product Data (item-specific)

  • Category Path: 全部 / 可售 / 生命科学
  • Research Use Note: For research use only

• General biochemical context (no clinical claims)

  • Pyridine motifs are prevalent in bioactive small molecules as hydrogen-bond acceptors and for tuning lipophilicity and pKa. The nicotinate scaffold (pyridine-3-carboxylate) relates structurally to nicotinic acid derivatives, though specific biological roles for this brominated, ethoxy-substituted ester are not established.
  • The ethyl ester functions as a protecting/transporting group in synthetic biology workflows, enabling later hydrolysis to the acid for conjugation to amines (amide formation) or further derivatization.
  • The 5-bromo substituent offers a late-stage diversification site via Pd-catalyzed coupling to rapidly generate SAR panels for enzyme/receptor screening in discovery research.

• Practical notes

  • Any biological testing should account for the compound’s hydrophobicity and potential for nonspecific binding due to the aryl bromide and ester; include appropriate controls and solvent blanks.
  • Not known to be a metabolite or cofactor; treat as a synthetic small-molecule research intermediate.

Buffer Applications

This product is a hydrophobic heteroaromatic building block, not a buffer component. It is not typically employed to prepare aqueous buffer systems.

• Guidance
  • For aqueous work, dissolve in a miscible organic co-solvent (e.g., DMSO, MeCN, EtOH) before spiking into buffer if needed for assays.
  • For actual buffering needs, select established systems (e.g., phosphate, HEPES, MOPS) appropriate to your pH range; this compound does not provide buffering capacity in the physiological range.

Green Alternatives

• Greener solvent choices for common transformations (general guidance)

  • Replace dioxane/toluene with 2-MeTHF or CPME for Pd-catalyzed couplings; these offer better safety and renewable sourcing (2-MeTHF).
  • Employ water/ethanol co-solvent systems for Suzuki couplings with appropriate bases and micellar catalysis where feasible.
  • Favor MeOH/EtOH over chlorinated solvents for ester hydrolysis or transesterification when compatible with the reaction.

• Comparison snapshot (general)

  • Dioxane vs 2-MeTHF: 2-MeTHF has a higher boiling point, partial water miscibility, and better green metrics; often maintains comparable coupling performance.
  • DCM vs EtOAc: EtOAc provides similar extraction/solvation utility with improved environmental profile.
  • DMF/DMAc vs Cyrene/PC: Consider bio-based dipolar aprotics (e.g., Cyrene) where solubility and catalyst tolerance permit.

• Waste and energy considerations

  • Electron-deficient pyridine couplings may proceed at lower catalyst loadings with modern ligands, reducing metal waste.
  • Continuous flow heating for couplings can enhance energy efficiency and safety.

• Note

  • Selection must be validated experimentally for your substrate pair and catalyst; heteroaromatic coordination can alter optimal conditions.

Pharmaceutical Uses

• Product Data (item-specific)

  • No pharmacopeial grade or excipient designation provided. Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.

• General, non-clinical context

  • Utilized as a synthetic intermediate in medicinal chemistry for the preparation of nicotinate-containing scaffolds. The aryl bromide allows rapid diversification for lead optimization.
  • Not intended for human or veterinary use; for research use only.
  • No recognized monograph in major pharmacopeias for this specific substituted nicotinate ester (literature/general observation).

• Development considerations

  • If scaling for GMP-intermediate manufacture, control halogenated impurities, residual palladium (if used), and establish robust ester hydrolysis/amidation steps with validated analytical methods.
  • Solubility and polymorphism (if crystalline) should be profiled early in process development.

Physical Properties

• Product Data (item-specific)

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet. (See computed value under literature.)

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

  • Estimated molecular formula: C10H12BrNO3
  • Computed molecular weight: ~274.12 g/mol
  • Expected physical form: crystalline solid or low-melting solid typical for aryl brominated pyridine esters (literature/general expectation; verify on CoA).
  • Solubility (qualitative, literature/general): good in common organic solvents (e.g., DCM, EtOAc, THF, MeCN, toluene); low in water due to aromaticity and ester/aryl bromide.
  • Volatility: low; non-volatile organic solid.

• General notes (chemistry background)

  • Polarity: moderately polar (heteroaromatic nitrogen and ester), yet largely organophilic.
  • UV absorbance: strong in 250–320 nm region typical for substituted pyridines and aryl bromides (qualitative; useful for HPLC/UV monitoring).
  • Refractive index, melting/boiling points, logP, pKa: Not specified for this item; consult literature or determine experimentally for your method development.

Quality and Grades

• Product Data (item-specific)

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

• Guidance on quality considerations (general)

  • For heteroaromatic building blocks, typical quality attributes include assay (HPLC/GC), identity (1H/13C NMR, MS), and residual solvents. Metal content is relevant if used in metal-sensitive catalysis or downstream API-enabling routes.
  • If used in cross-coupling, low halogen scrambling/byproducts and minimal protodebromination impurities are beneficial for clean conversions.
  • If UV-based analytics are used, knowledge of chromophoric impurities aids method development; “HPLC grade” is a solvent term and not applicable here.
  • Stabilizers: None indicated for this item. If stabilizers are used in related products, they can influence reactivity and analysis—verify on CoA when critical.

• Documentation

  • For specific assay, impurity profile, residual solvent limits, water content, and melting range: Not specified for this item; refer to CoA/Spec Sheet.

Reaction and Applications

• Use profile (general for this scaffold)

  • A versatile heteroaromatic building block combining an aryl bromide (5-position), an ethyl ester at the 3-position, and a ring nitrogen. The 2-ethoxy substituent modulates electronics and can be transformed under specific conditions.

• Typical transformations (literature/general)

  • Cross-coupling at C5–Br: Suzuki–Miyaura (with aryl/heteroaryl/vinyl boron species), Buchwald–Hartwig amination (install amines), Sonogashira (alkynes), Negishi/Stille/Kumada (C–C formation).
  • Ester chemistry at C3: Hydrolysis to the acid (then amide formation), alcohol formation by reduction (DIBAL-H to aldehyde; LiAlH4 to primary alcohol), or transesterification.
  • Halogen–metal exchange: Conversion to organolithium or Grignard (care with pyridine N coordination) for subsequent electrophile trapping.
  • Ring nitrogen manipulations: N-oxidation (pyridine N-oxide) to alter directing effects; N-quaternization for ionic derivatives.
  • Ethoxy at C2: Acidic or Lewis-acid-promoted dealkylation to the corresponding 2-hydroxynicotinate may be feasible; stronger nucleophiles can effect substitution under SNAr-like conditions when activated.

• Application areas (non-clinical, discovery-centric)

  • Intermediate for agrochemical and pharmaceutical discovery programs where a 3-nicotinate core is decorated at C5 via Pd-catalysis.
  • Useful in SAR libraries exploiting pyridine’s H-bond acceptor character and the ortho-ethoxy’s steric/electronic tuning.

• Practical tips

  • For couplings on electron-deficient pyridines, use ligands tolerant of heteroaromatics (e.g., SPhos/XPhos/BrettPhos) and bases such as K3PO4, Cs2CO3, or K2CO3; control for protodebromination.
  • Dry, oxygen-free conditions generally improve yields; pre-activation and base choice are key with sensitive partners.

Reaction Conditions

The following are literature-style, general conditions for similar substrates; optimize for your system. Not item specifications.

• Suzuki–Miyaura coupling (C5–Br to C5–Ar)

  • Catalyst: Pd(PPh3)4 (1–3 mol%) or Pd-precursor with SPhos/XPhos (1–2 mol% Pd)
  • Base: K3PO4, K2CO3, or Cs2CO3 (2–3 eq)
  • Solvent: 1,4-dioxane/water (3:1), 2-MeTHF/water, or toluene/EtOH/water
  • Temperature: 70–100 °C; Time: 2–16 h; Typical isolated yields: 60–90% (substrate-dependent)

• Buchwald–Hartwig amination (C5–Br to C5–NR2)

  • Catalyst/ligand: Pd2(dba)3 (1 mol% Pd) + BrettPhos or XPhos; or Pd(OAc)2 + t-BuBrettPhos
  • Base: NaOtBu or K3PO4; Solvent: toluene, dioxane, or 2-MeTHF
  • Temperature: 80–110 °C; Time: 4–18 h; Yields often 50–85%

• Sonogashira coupling (C5–Br to C5–C≡C–R)

  • Catalyst: Pd(PPh3)2Cl2 (1–2 mol%), CuI (5–10 mol%)
  • Base: Et3N or i-Pr2NH; Solvent: THF, Et3N, or DMF; 25–80 °C, 2–12 h

• Ester hydrolysis (to 3-nicotinic acid)

  • Conditions: Aqueous NaOH or K2CO3 in MeOH/H2O or THF/H2O (0–60 °C); Acidic workup to isolate acid; Often quantitative.

• DIBAL-H reduction (to aldehyde)

  • Solvent: dry toluene or THF; Temperature: −78 to −20 °C; Quench carefully with MeOH/H2O at low temperature.

• Notes

  • Exclude air/moisture for Pd-catalyzed reactions. The pyridine nitrogen can coordinate and may require ligand tuning and base selection to maintain catalyst activity.

Safety and Handling

• Product Data (item-specific)

  • Storage Conditions: Room temperature
  • Hazard Information: Signal Word: Not specified; H-Statements: Not specified; GHS Classification: Not specified; Pictograms: Not specified. Refer to the SDS for authoritative safety information.

• General safety guidance (for heteroaromatic bromides/esters; not a substitute for SDS)

  • Likely hazards: May cause skin/eye/respiratory irritation; avoid dust formation and inhalation. Handle in a fume hood.
  • PPE: Safety glasses or goggles, lab coat, appropriate chemical-resistant gloves (e.g., nitrile). Use respiratory protection if dust/aerosols could form and adequate ventilation is not available.
  • Incompatibilities: Strong bases/acids can hydrolyze the ester; strong nucleophiles under forcing conditions may displace the ethoxy on the ring; avoid strong oxidizers/reducers that may affect the aryl bromide.
  • Fire safety: Organic solid; keep away from ignition sources. Use CO2, dry chemical, or foam for small fires.
  • First aid overview: Eye/skin contact—rinse with water for at least 15 minutes; remove contaminated clothing. Inhalation—move to fresh air. Ingestion—rinse mouth; do not induce vomiting; seek medical attention.
  • Spill response: Avoid dust, collect mechanically or with inert absorbent, dispose per local regulations.

Always consult and follow the product-specific SDS for definitive hazard, exposure limits, and emergency procedures.

Solvent Selection

This compound is a moderately polar, organophilic heteroaromatic ester; solvent choice is typically driven by reaction class (e.g., coupling, hydrolysis, amidation) and solubility of partners.

• General miscibility/solubility (literature/general)

  • Good solubility in EtOAc, DCM, THF, MeCN, toluene, DMF/DMAc, dioxane; poor solubility in water.

• Selection by application (general)

  • Cross-coupling (Suzuki/Negishi/Buchwald–Hartwig): 1,4-dioxane, toluene, THF, CPME, or 2-MeTHF; consider water/EtOH co-solvent for Suzuki with inorganic bases.
  • Ester transformations (hydrolysis, amidation): MeOH/EtOH with base or acid for hydrolysis; DMF/MeCN/THF for coupling to amides (EDC/HATU/DIC systems) when converting the ester via activation.
  • Reductions (to alcohol): THF or MeOH with DIBAL-H/NaBH4 (via activation) depending on route.

• Practical notes

  • The pyridine nitrogen may coordinate to metals; polar aprotic solvents (DMF, MeCN) can improve catalyst solubility but may slow some couplings; ligand choice compensates.
  • Maintain anhydrous solvents for moisture-sensitive operations (e.g., metal–halogen exchange, Pd-couplings with base-sensitive partners).

• Quick comparison (general)

  • THF/2-MeTHF: good solubilizing power; 2-MeTHF preferred for greener profiles and higher bp.
  • Dioxane: robust for couplings but with safety/green concerns; use alternatives if possible.
  • DMF/DMAc: excellent solubility for polar substrates; consider high-boiling workup and safety aspects.

Storage and Reconstitution

• Product Data (item-specific)

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

• Storage guidance (general best practices for heteroaromatic esters)

  • Keep container tightly closed in a dry, well-ventilated place. Use an inert atmosphere (e.g., nitrogen) if storing long-term to minimize hydrolysis or oxidation.
  • Protect from prolonged exposure to moisture and strong light; esters can hydrolyze under humid/basic conditions.
  • Segregate from strong acids/bases and strong oxidizers.

• Reconstitution/handling

  • If supplied as a solid, dissolve in dry organic solvents (e.g., DCM, THF, MeCN, EtOAc) to prepare stock solutions. If solutions are prepared, store at 2–8 °C and use within a few days, or freeze aliquots to avoid repeated freeze–thaw.
  • Concentrate solutions under reduced pressure at ≤40 °C to avoid decomposition; co-evaporate with anhydrous toluene/EtOH if needed to remove high-boiling solvents.

• Stability notes

  • No stabilizer is indicated for this item. Monitor purity by HPLC/LC–MS over time if stored in solution.
  • For definitive shelf-life and stability data: Not specified for this item; refer to CoA/Spec Sheet.

Structure and Identity

Brief description: Ethyl 5-bromo-2-ethoxynicotinate is a halogenated, ethoxy-substituted nicotinate ester on a pyridine core, offering an aryl bromide cross-coupling handle and a tunable ester.

• Product Data (item-specific)

  • SKU: E1034736
  • Product Name: Ethyl 5-bromo-2-ethoxynicotinate
  • CAS: 1310416-59-1
  • PubChem CID: 74889502
  • InChIKey: 407362 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

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

  • Core scaffold: nicotinate (pyridine-3-carboxylate) esterified with ethyl at C3
  • Substitution pattern: 2-ethoxy, 5-bromo on the pyridine ring
  • Functional groups: pyridine N, aryl bromide, ethyl ester (carboxylate), aryl ethoxy ether
  • Molecular formula (computed from name): C10H12BrNO3
  • Molecular weight (computed): ~274.12 g/mol

• Structural description (2D, words; general)

  • A six-membered aromatic pyridine ring (one ring nitrogen). The carboxylate at the 3-position is an ethyl ester (–CO2Et). The 2-position bears an ethoxy substituent (–OCH2CH3). The 5-position carries bromine. No stereocenters; planar heteroaromatic system.

Synthetic Utility

• Orthogonal handles

  • C5–Br: Excellent handle for Pd-catalyzed C–C/C–N/C–O couplings, and for metal–halogen exchange to access 5-functionalized nicotinates.
  • C3–CO2Et: Convertible via hydrolysis to acid, amidation (after activation), or reduction to alcohol/aldehyde, enabling vector changes on the ring.
  • Pyridine N: Coordination site that can direct metalation or be oxidized (N-oxide) to alter reactivity and regioselectivity.
  • C2–OEt: Potentially transformable to 2-hydroxy or other substituents under SNAr/Lewis-acid or demethylation-like conditions.

• Retrosynthetic value (general)

  • Serves as a convergent node: install diversity at C5 last via cross-coupling while keeping the ester intact; later unmask the acid for coupling to amines/alcohols.

• Named reaction relevance

  • Suzuki–Miyaura, Buchwald–Hartwig, Sonogashira, Stille/Negishi/Kumada couplings at C5.
  • DIBAL-H reductions of esters to aldehydes; LiAlH4 to primary alcohols; saponification/transesterification for functional handle exchange.

• Practical insights

  • Heteroaromatic coordination may inhibit catalysis; employ heteroarene-tolerant ligands, higher base strength, and controlled temperatures.
  • Protect acid-labile partners; the ester is generally stable to bases used in couplings but can hydrolyze under strong aqueous base or acid.

Target Specificity

Not applicable. This product is a small-molecule chemical building block, not a biological macromolecule or targeted reagent. No antigen/epitope, species reactivity, clone, or isotype data apply.