Production Method 1

202865-72-3

959996-48-6

Reaction Conditions

1.1 Reagents: Chloro(1-methylethyl)magnesium Solvents: Tetrahydrofuran ;  -42 °C; 2 h, -42 °C
1.2 Reagents: Triisopropyl borate ;  -42 °C → rt; overnight, rt
1.3 Reagents: Sodium hydroxide Solvents: Water ;  rt
1.4 Reagents: Hydrochloric acid Solvents: Water ;  pH 3

Reference

Discovery of (R)-4-Cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-Cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007): Metabolically Stable γ-Secretase Inhibitors that Selectively Inhibit the Production of Amyloid-β over Notch

Probst, Gary; Aubele, Danielle L.; Bowers, Simeon; Dressen, Darren; Garofalo, Albert W.; et al, Journal of Medicinal Chemistry, 2013, 56(13), 5261-5274

Production Method 2

202865-72-3

959996-48-6

Reaction Conditions

1.1 Reagents: Chloro(1-methylethyl)magnesium Solvents: Tetrahydrofuran ;  -42 °C; 2 h, -42 °C
1.2 Reagents: Triisopropyl borate ;  -42 °C → rt; overnight, rt
1.3 Reagents: Sodium hydroxide Solvents: Water ;  1 h, rt
1.4 Reagents: Hydrochloric acid Solvents: Water ;  pH 3

Reference

Preparation of fused tricyclic sulfonamides, especially 5-arylsulfonyl-1H-pyrazolo[4,3-c]quinolines, as gamma-secretase inhibitors for the treatment of cognitive disorders

, World Intellectual Property Organization, , ,

(2-Bromo-5-fluorophenyl)boronic acid Raw materials

• 1-Bromo-4-fluoro-2-iodobenzene

(2-Bromo-5-fluorophenyl)boronic acid Preparation Products

• (2-Bromo-5-fluorophenyl)boronic acid (959996-48-6)

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• Solvents and Organic Chemicals Organic Compounds Benzenoids Benzene and substituted derivatives Halobenzenes Fluorobenzenes

Introduction to (2-Bromo-5-fluorophenyl)boronic Acid (CAS No. 959996-48-6)

(2-Bromo-5-fluorophenyl)boronic acid is a specialized organoboron compound that has garnered significant attention in the field of pharmaceutical and materials chemistry due to its versatile applications. This compound, identified by the CAS number 959996-48-6, is a key intermediate in the synthesis of various high-value chemicals, particularly in the development of novel therapeutic agents and advanced materials. Its unique structural features, combining both bromine and fluorine substituents on a phenyl ring, make it a valuable building block for further functionalization and derivatization.

The significance of (2-Bromo-5-fluorophenyl)boronic acid lies in its role as a precursor in cross-coupling reactions, which are fundamental to modern synthetic organic chemistry. Specifically, its boronic acid moiety allows for participation in Suzuki-Miyaura couplings, a widely used method for forming carbon-carbon bonds. This reaction is particularly crucial in the pharmaceutical industry for constructing complex molecular architectures. The presence of both bromine and fluorine atoms on the aromatic ring enhances its reactivity and selectivity, making it an ideal candidate for tailored synthetic pathways.

In recent years, there has been a surge in research focused on developing new methodologies for the functionalization of aryl rings. The combination of bromine and fluorine in (2-Bromo-5-fluorophenyl)boronic acid provides a unique opportunity to explore such transformations. For instance, recent studies have demonstrated its utility in the synthesis of fluorinated heterocycles, which are known to exhibit enhanced biological activity and metabolic stability. These findings have opened up new avenues for drug discovery, particularly in the quest for more effective antiviral and anticancer agents.

The boronic acid functional group in this compound is particularly noteworthy due to its ability to engage in coordination with various metal catalysts. This property has been leveraged in the development of transition-metal-catalyzed reactions that facilitate the introduction of diverse substituents onto the aromatic core. Such transformations are essential for creating structurally diverse libraries of compounds, which are often required for high-throughput screening campaigns in drug discovery programs. The modular nature of (2-Bromo-5-fluorophenyl)boronic acid allows chemists to systematically explore different chemical space with relative ease.

Moreover, the electronic properties imparted by the bromine and fluorine substituents influence the reactivity of the boronic acid group. For example, electron-withdrawing effects from these halogens can enhance the electrophilicity of the boron center, thereby facilitating its participation in nucleophilic addition reactions. This has been exploited in recent synthetic strategies where (2-Bromo-5-fluorophenyl)boronic acid serves as a key intermediate in constructing biaryl frameworks, which are prevalent in many biologically active molecules.

The pharmaceutical industry has been particularly keen on exploring derivatives of this compound due to their potential therapeutic applications. Researchers have reported novel scaffolds derived from (2-Bromo-5-fluorophenyl)boronic acid that exhibit promising biological activity against various targets. These include enzymes involved in inflammatory pathways and receptors implicated in neurological disorders. The ability to fine-tune the electronic and steric properties of these derivatives through further functionalization has made this compound a cornerstone in medicinal chemistry.

In addition to its pharmaceutical relevance, (2-Bromo-5-fluorophenyl)boronic acid has found applications in materials science. Its incorporation into polymers and coatings can impart unique properties such as enhanced thermal stability or optical activity. Recent advances in polymer chemistry have demonstrated its utility in creating functionalized polymers that exhibit improved performance characteristics. These materials are being explored for use in electronics, aerospace, and biomedical devices, highlighting the broad utility of this compound beyond traditional organic synthesis.

The synthesis of (2-Bromo-5-fluorophenyl)boronic acid itself is an area of active research. While several methods have been reported, continuous improvements are being sought to enhance yield and purity while minimizing environmental impact. Modern synthetic approaches often involve palladium-catalyzed cross-coupling reactions starting from readily available precursors. Such methodologies align with the growing emphasis on sustainable chemistry practices within the industry.

The future prospects for (2-Bromo-5-fluorophenyl)boronic acid are vast, driven by ongoing advancements in synthetic chemistry and an increasing demand for specialized intermediates. As our understanding of structure-activity relationships continues to evolve, new applications will undoubtedly emerge. The compound's unique combination of reactivity and functionality ensures its continued relevance as a critical building block in both academic research and industrial settings.

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