5-Bromo-3-fluoro-2-methoxyaniline: Properties & Lab Guide

5-bromo-3-fluoro-2-methoxyaniline is a halogenated aromatic amine building block widely used in medicinal chemistry and pharmaceutical synthesis owing to its combination of bromo, fluoro, and methoxy substituents on the aniline scaffold.

Chemical Name

5-bromo-3-fluoro-2-methoxyaniline

CAS Number

Needs review — not confirmed in source material

Molecular Formula

C7H7BrFNO

Molecular Weight

220.04 g/mol

Key Functional Groups

Primary amine (–NH2), bromo (–Br), fluoro (–F), methoxy (–OCH3)

SKU

B635824

Primary Application

Pharmaceutical intermediate and medicinal chemistry building block

Chemical Identity and Physical Properties

5-Bromo-3-fluoro-2-methoxyaniline (Aladdin SKU: B635824) is an ortho-methoxy-substituted aniline bearing bromine at the 5-position and fluorine at the 3-position of the aromatic ring. Its molecular formula is C₇H₇BrFNO with a molecular weight of approximately 220.04 g/mol.

The compound features three distinct substituents that confer complementary reactivity: the free primary amine (–NH₂) serves as a versatile handle for amide coupling, diazotization, and reductive amination reactions; the aryl bromide enables transition-metal-catalyzed cross-coupling reactions (e.g., Suzuki, Buchwald–Hartwig, and Sonogashira couplings); and the aryl fluoride can participate in nucleophilic aromatic substitution under appropriate conditions. The methoxy group acts as an electron-donating substituent that modulates the ring electron density and can influence regioselectivity in subsequent transformations.

Physical appearance is typically a solid or low-melting solid at room temperature. Specific melting point, boiling point, density, and solubility data should be confirmed against the current certificate of analysis (CoA) provided by Aladdin Scientific.

Synthesis Relevance and Pharmaceutical Applications

Halogenated anilines bearing multiple substituents such as 5-bromo-3-fluoro-2-methoxyaniline are highly valued in drug discovery and process chemistry. The co-presence of aryl bromide and aryl fluoride on the same ring provides synthetic flexibility: chemists can exploit orthogonal reactivity—selectively engaging the C–Br bond under palladium catalysis while preserving the C–F bond for a subsequent step, or leveraging the C–F bond in a SNAr step independently of the C–Br bond.

The primary amine functionality makes this compound a direct precursor to pharmaceutically relevant amide, urea, sulfonamide, and heterocyclic motifs. Diazotization of the amine followed by Sandmeyer reactions offers routes to the corresponding aryl nitrile, aryl halide, or aryl hydroxyl derivatives, expanding the synthetic reach of this building block considerably.

In medicinal chemistry, fluorine substitution on aromatic rings is a widely employed strategy to improve metabolic stability, membrane permeability, and binding affinity of drug candidates. The methoxy group contributes additional lipophilicity tuning and can serve as a masked phenol upon demethylation. Collectively, these features position 5-bromo-3-fluoro-2-methoxyaniline as a versatile scaffold for the construction of kinase inhibitors, GPCR ligands, and other bioactive small molecules.

Handling, Safety, and Storage Guidelines

Personal Protective Equipment (PPE): Aromatic amines as a chemical class may present health hazards including skin sensitization and potential mutagenicity. Always handle 5-bromo-3-fluoro-2-methoxyaniline wearing appropriate PPE: chemical-resistant gloves (nitrile or equivalent), a laboratory coat, and eye protection. Conduct all weighing and transfers in a well-ventilated fume hood to minimize inhalation exposure to dust or vapors.

Storage: Store the reagent in a tightly sealed container in a cool, dry location away from light, moisture, heat sources, and incompatible materials (strong oxidizers, strong acids). Recommended storage temperature is typically 2–8 °C or room temperature under inert atmosphere; consult the current CoA and SDS supplied by Aladdin Scientific for compound-specific conditions.

Disposal: Dispose of waste material in accordance with local, regional, and national regulations governing halogenated organic compounds. Do not pour down the drain. Consult your institution's environmental health and safety (EHS) office for guidance.

Note: Specific GHS hazard classifications, first-aid measures, and regulatory identifiers for this compound should be verified in the Safety Data Sheet (SDS) available from Aladdin Scientific prior to use.

Recommended Reaction Conditions and Tips

Solubility: Halogenated methoxyanilines are generally soluble in common organic solvents including dichloromethane (DCM), tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), ethyl acetate, and acetonitrile. Aqueous solubility is limited at neutral pH but may increase under acidic conditions due to protonation of the amine. Solubility should be empirically verified prior to large-scale use.

Palladium-Catalyzed Cross-Coupling (C–Br bond): The aryl bromide in this compound is reactive toward standard Pd(0)/Pd(II) catalytic systems. For Suzuki–Miyaura coupling, Pd(PPh₃)₄ or Pd(dppf)Cl₂ with an inorganic base (K₂CO₃, Cs₂CO₃) in dioxane/water at 80–100 °C are typical starting conditions. For Buchwald–Hartwig amination, bulky phosphine ligands (e.g., BINAP, XPhos) are recommended. Reactions should be conducted under inert atmosphere (N₂ or Ar).

Amide and Urea Formation (–NH₂): The aniline nitrogen can be acylated using acyl chlorides or activated esters (e.g., NHS esters) in the presence of a base such as triethylamine or DIPEA in DCM or THF. Isocyanates react directly with the aniline to afford ureas without additional activation.

Stability Considerations: Protect from prolonged exposure to air and moisture. Oxidation of the free amine is possible upon extended storage. Prepare solutions freshly when possible or store stock solutions under inert gas at –20 °C.

Frequently asked questions

What is the CAS number for 5-bromo-3-fluoro-2-methoxyaniline?

The CAS number for 5-bromo-3-fluoro-2-methoxyaniline was not confirmed in the source material provided. Please refer to the product page for Aladdin SKU B635824 or the accompanying Certificate of Analysis for the verified CAS registry number.

Which cross-coupling reactions are compatible with 5-bromo-3-fluoro-2-methoxyaniline?

The aryl bromide position is reactive in palladium-catalyzed Suzuki–Miyaura, Buchwald–Hartwig, Sonogashira, and Negishi cross-coupling reactions under standard conditions. The aryl fluoride bond is less reactive under these conditions but can be engaged in nucleophilic aromatic substitution with strong nucleophiles, providing orthogonal synthetic handles on the same molecule.

How should 5-bromo-3-fluoro-2-methoxyaniline be stored to maintain stability?

Store the compound in a tightly sealed container under cool, dry, and light-protected conditions, preferably at 2–8 °C or under inert atmosphere. Free aromatic amines can be susceptible to oxidative degradation upon prolonged air exposure, so minimize headspace and consider backfilling with nitrogen or argon. Always consult the SDS and CoA from Aladdin Scientific for compound-specific storage recommendations.

Is 5-bromo-3-fluoro-2-methoxyaniline suitable for amide bond formation?

Yes. The primary aniline (–NH2) group readily undergoes acylation with acyl chlorides, anhydrides, or carboxylic acids activated by coupling reagents (such as HATU or EDC) to form secondary anilide products. A non-nucleophilic base such as triethylamine or DIPEA is typically used to neutralize the acid generated during the reaction.

What purity grade is available for Aladdin's 5-bromo-3-fluoro-2-methoxyaniline (B635824)?

Purity specification details for B635824 were not explicitly stated in the provided source material. Please visit the Aladdin Scientific product page for SKU B635824 or request the current Certificate of Analysis to confirm purity grade, analytical method, and lot-specific data.

References

1. Aladdin Scientific. Product page: 5-bromo-3-fluoro-2-methoxyaniline, SKU B635824. Aladdin Scientific Corp.
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. (General reference for aromatic amine and cross-coupling chemistry.)
3. Roughley, S. D.; Jordan, A. M. The medicinal chemist's toolbox: an analysis of reactions used in the pursuit of drug candidates. J. Med. Chem. 2011, 54, 3451–3479. doi:10.1021/jm200187y
4. Hagmann, W. K. The many roles of fluorine in medicinal chemistry. J. Med. Chem. 2008, 51, 4359–4369. doi:10.1021/jm800219f

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