Chemical Identity and Properties

Methyl 4-bromoquinoline-8-carboxylate (SKU: M726066) is a halogenated bicyclic heteroaromatic compound featuring a quinoline core. The molecule bears a bromine atom at the 4-position and a methyl ester functionality at the 8-position, making it a bifunctional building block well-suited for sequential or orthogonal synthetic transformations.

The C-4 carbon–bromine bond is activated toward oxidative addition into palladium(0) and other transition-metal catalysts, enabling efficient participation in Suzuki–Miyaura, Negishi, Stille, and Buchwald–Hartwig cross-coupling reactions. The peri-positioned methyl ester at C-8 can be further elaborated via hydrolysis, reduction, or amidation, providing additional synthetic handles for library synthesis and lead optimization campaigns in drug discovery.

The quinoline scaffold itself is a privileged structure in medicinal chemistry, appearing in numerous approved pharmaceuticals and natural products. Researchers should consult the product's Safety Data Sheet (SDS) for precise physicochemical data including molecular weight, melting point, and solubility, as these values require verification against the current certificate of analysis.

Safe Handling and Storage

Personal Protective Equipment (PPE): Always handle Methyl 4-bromoquinoline-8-carboxylate in a chemical fume hood. Wear nitrile gloves, a laboratory coat, and chemical splash goggles. In case of skin contact, wash immediately with soap and water for at least 15 minutes. In case of eye contact, flush with copious water and seek medical attention.

Storage Conditions: Store the compound in a tightly sealed container in a cool (2–8 °C recommended), dry, and well-ventilated area, away from direct light and incompatible materials such as strong oxidizers and strong bases. After first opening, transfer remaining material to an inert atmosphere (nitrogen or argon) to prevent hydrolysis of the ester moiety and adventitious moisture uptake.

Waste Disposal: Dispose of all waste material containing this compound in accordance with applicable local, regional, and national regulations. Do not pour halogenated organic compounds down the drain. Consult your institution's Environmental Health and Safety (EHS) office for guidance on halogenated waste streams.

Note: Specific hazard classifications (GHS pictograms, H-statements, P-statements) must be confirmed from the current SDS available from Aladdin Scientific prior to use.

Recommended Synthetic Applications and Protocol

Methyl 4-bromoquinoline-8-carboxylate is most commonly employed as an electrophilic coupling partner in transition-metal-catalyzed cross-coupling reactions. The general workflow below outlines a representative Suzuki–Miyaura coupling as a starting point; researchers should optimize reaction conditions for their specific substrate and target.

General Suzuki–Miyaura Coupling Procedure (Representative):

1. Charge a dry, inert-atmosphere Schlenk flask or sealed vial with Methyl 4-bromoquinoline-8-carboxylate (1.0 equiv), the desired aryl- or heteroarylboronic acid or pinacol boronate ester (1.2–1.5 equiv), and a suitable palladium catalyst (e.g., Pd(PPh₃)₄ or Pd(dppf)Cl₂, 2–5 mol%).
2. Add a base (e.g., K₂CO₃ or Cs₂CO₃, 2.0–3.0 equiv) and a solvent system appropriate for Suzuki coupling (e.g., DMF/H₂O, dioxane/H₂O, or toluene/EtOH/H₂O mixtures).
3. Degas the reaction mixture by three freeze-pump-thaw cycles or by sparging with nitrogen/argon for 15 minutes.
4. Stir the reaction at 80–100 °C for 6–18 hours under inert atmosphere, monitoring progress by TLC or LC-MS.
5. Upon completion, cool to room temperature, dilute with ethyl acetate, wash with water and brine, dry over anhydrous MgSO₄ or Na₂SO₄, filter, and concentrate under reduced pressure.
6. Purify the crude product by silica gel column chromatography (gradient elution with hexanes/ethyl acetate) or by preparative HPLC as appropriate.

Caution: All catalyst loadings, temperatures, solvents, and reaction times are approximate starting points. Optimization is required for each specific coupling partner. Verify all conditions against current literature before use.

Quality Control and Analytical Verification

Prior to use in sensitive synthetic sequences, researchers are advised to verify the identity and purity of Methyl 4-bromoquinoline-8-carboxylate using the following analytical approaches:

• ¹H NMR Spectroscopy: Confirm the characteristic aromatic proton signals of the quinoline ring system and the singlet corresponding to the methyl ester (–OCH₃) group. The absence of the C-4 H signal (replaced by bromine) serves as a key structural marker.
• ¹³C NMR Spectroscopy: Verify the carbonyl carbon of the methyl ester and the carbon bearing the bromine substituent at C-4.
• HPLC Purity: Run a reversed-phase HPLC analysis (C18 column, acetonitrile/water gradient) to confirm purity ≥95% or as specified on the Certificate of Analysis (CoA).
• LC-MS or HRMS: Confirm the molecular ion consistent with the expected molecular formula and the characteristic bromine isotope pattern (M and M+2 in approximately 1:1 ratio).
• Melting Point: Measure and compare against the value stated on the CoA.

Always request and review the current Certificate of Analysis (CoA) from Aladdin Scientific for each lot prior to use. Store CoA documentation with your experimental records for traceability.