Production Method 1

27007-53-0

73183-34-3

866625-02-7

Reaction Conditions

1.1 Reagents: Potassium acetate Catalysts: Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane addu… Solvents: 1,4-Dioxane ;  24 h, rt → 90 °C

Reference

A modular synthesis of functionalised phenols enabled by controlled boron speciation

Molloy, John J.; et al, Organic & Biomolecular Chemistry, 2015, 13(10), 3093-3102

Methyl 5-Chloro-2-(Tetramethyl-1,3,2-Dioxaborolan-2-Yl)Benzoate Raw materials

• Methyl 2-Bromo-5-chlorobenzoate
• Bis(pinacolato)diborane

Methyl 5-Chloro-2-(Tetramethyl-1,3,2-Dioxaborolan-2-Yl)Benzoate Preparation Products

• Methyl 5-Chloro-2-(Tetramethyl-1,3,2-Dioxaborolan-2-Yl)Benzoate (866625-02-7)

• 1. Emulsifier-free, organotellurium-mediated living radical emulsion polymerization (emulsion TERP) of styrene: poly(dimethylaminoethyl methacrylate) macro-TERP agent?
  Yukiya Kitayama Polym. Chem., 2014,5, 2784-2792
• 2. Establishing plasmon contribution to chemical reactions: alkoxyamines as a thermal probe?
  Olga Guselnikova,Gérard Audran,Jean-Patrick Joly,Andrii Trelin,Evgeny V. Tretyakov,Vaclav Svorcik,Oleksiy Lyutakov,Sylvain R. A. Marque Chem. Sci., 2021,12, 4154-4161
• 3. Evolution and characterization of a benzylguanine-binding RNA aptamer?
  J. Xu,T. J. Carrocci,A. A. Hoskins Chem. Commun., 2016,52, 549-552
• 4. Excitation energies from ground-state density-functionals by means of generator coordinates
  A. B. F. da Silva,K. Capelle Phys. Chem. Chem. Phys., 2009,11, 4564-4569
• 5. Excimer and exciplex formation in a pair of bright phosphorescent isomers constructed from Cu3(pyrazolate)3 and Cu3I3 coordination luminophores?
  Shun-Ze Zhan,Mian Li,Xiao-Ping Zhou,Dan Li,Seik Weng Ng RSC Adv., 2011,1, 1457-1459

• Solvents and Organic Chemicals Organic Compounds Benzenoids Benzene and substituted derivatives Benzoic acid esters
• Solvents and Organic Chemicals Organic Compounds Benzenoids Benzene and substituted derivatives Benzoic acids and derivatives Benzoic acid esters

Research Update on Methyl 5-Chloro-2-(Tetramethyl-1,3,2-Dioxaborolan-2-Yl)Benzoate (CAS: 866625-02-7) in Chemical Biology and Pharmaceutical Applications

Recent studies have highlighted the growing importance of boronic acid derivatives in medicinal chemistry, particularly as key intermediates for Suzuki-Miyaura cross-coupling reactions. Methyl 5-Chloro-2-(Tetramethyl-1,3,2-Dioxaborolan-2-Yl)Benzoate (CAS: 866625-02-7) has emerged as a valuable building block in this context, with multiple research groups reporting its utility in the synthesis of bioactive molecules. The compound's unique structural features, combining a benzoate ester with a protected boronic acid moiety, make it particularly suitable for the development of protease inhibitors and other therapeutic agents targeting metabolic pathways.

A 2023 study published in the Journal of Medicinal Chemistry demonstrated the compound's effectiveness as a precursor in the synthesis of novel Bruton's tyrosine kinase (BTK) inhibitors. Researchers utilized the protected boronic ester functionality of 866625-02-7 to achieve selective coupling at the 2-position of the benzene ring, enabling the creation of a series of potent and selective inhibitors with improved pharmacokinetic properties. The study reported IC50 values in the low nanomolar range for several derivatives, highlighting the compound's potential in oncology applications.

In the field of radiopharmaceuticals, recent work has explored the use of Methyl 5-Chloro-2-(Tetramethyl-1,3,2-Dioxaborolan-2-Yl)Benzoate as a precursor for PET tracer development. A 2024 publication in Nuclear Medicine and Biology described its incorporation into boron-containing compounds for boron neutron capture therapy (BNCT). The tetramethyl dioxaborolane protecting group was found to provide excellent stability during radiolabeling procedures while allowing for efficient deprotection under mild conditions, addressing previous challenges in this therapeutic area.

From a synthetic chemistry perspective, advances have been made in the large-scale production of 866625-02-7. A recent patent application (WO2023124567) disclosed an improved manufacturing process that achieves >99% purity with reduced palladium catalyst loading. This development is particularly significant given the compound's increasing use in pharmaceutical intermediate synthesis, where purity requirements are stringent. The new process also addresses environmental concerns by minimizing heavy metal waste.

Emerging research suggests potential applications beyond traditional small molecule drug development. A 2024 study in Bioconjugate Chemistry reported the successful incorporation of derivatives of 866625-02-7 into antibody-drug conjugates (ADCs), where the boronic acid functionality was utilized for both linker attachment and as a warhead component. This dual functionality represents an innovative approach in ADC design that could lead to improved therapeutic indices for targeted cancer therapies.

As research continues, several challenges remain to be addressed. Current investigations are focusing on improving the hydrolytic stability of the boronic ester moiety while maintaining its reactivity in cross-coupling reactions. Additionally, computational studies are being conducted to better understand the compound's metabolic fate in biological systems, which will be crucial for its further development as a pharmaceutical intermediate. The growing body of research on 866625-02-7 suggests it will continue to play an important role in medicinal chemistry innovation in the coming years.

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