3-(Benzyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine
[CAS# 1375302-99-0]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound
• Name: 3-(Benzyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine
• Synonyms: 3-phenylmethoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine
• Molecular Formula: C₁₈H₂₂BNO₃
• Molecular Weight: 311.18
• CAS Registry Number: 1375302-99-0
• EC Number: 815-537-3
• SMILES: B1(OC(C(O1)(C)C)(C)C)C2=CC(=CN=C2)OCC3=CC=CC=C3

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 451.5±35.0 ºC 760 mmHg (Calc.)^*
• Flash point: 226.9±25.9 ºC (Calc.)^*
• Index of refraction: 1.544 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H332-H335
• Precautionary Statements: P261-P280-P305+P351+P338

Discovory and Applicatios

3-(Benzyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine is a boronic ester derivative that plays a role as an intermediate in the field of synthetic organic chemistry, particularly in cross-coupling reactions. The compound is structurally composed of a substituted pyridine ring bearing two significant functional groups: a benzyloxy substituent at the 3-position and a boronic ester moiety at the 5-position. The boronic ester is present as a pinacol ester, which is a common and stable form used in organoboron chemistry.

This compound is typically synthesized through borylation reactions involving halogenated pyridine precursors. A common method starts from 3-hydroxy-5-bromopyridine, which undergoes benzylation using benzyl bromide under basic conditions to afford the corresponding benzyloxy derivative. Subsequent palladium-catalyzed borylation with bis(pinacolato)diboron (B₂pin₂) affords the target boronic ester. The use of Pd(dppf)Cl₂ or similar catalysts under mild conditions ensures regioselective substitution at the halogenated position, yielding high-purity products.

3-(Benzyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine is primarily used as a coupling partner in Suzuki–Miyaura cross-coupling reactions. The pinacol boronic ester group is reactive under standard cross-coupling conditions, where it forms a carbon–carbon bond with various aryl or vinyl halides in the presence of a palladium catalyst and a base. This transformation is widely utilized in the synthesis of more complex heteroaryl structures and is especially valuable in the pharmaceutical industry for constructing biaryl frameworks found in active pharmaceutical ingredients.

The presence of the benzyloxy group on the pyridine ring introduces a protected phenolic functionality. This protection ensures chemical stability during reaction sequences and can be removed under hydrogenolysis conditions using palladium on carbon with hydrogen gas, releasing the corresponding phenol. The ability to control the timing of deprotection is useful for orthogonal protection strategies in multi-step synthesis.

Applications of compounds derived from 3-(benzyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine span the development of agrochemicals, pharmaceuticals, and materials science. In medicinal chemistry, substituted pyridines are frequently found in kinase inhibitors, anti-inflammatory agents, and neuroactive compounds. The boronic ester enables rapid access to diverse analogs through modular coupling strategies, facilitating structure–activity relationship (SAR) studies.

The incorporation of a pyridine core also offers coordination ability, allowing interaction with metal centers or enzyme active sites. Therefore, derivatives synthesized from this compound can serve as ligands or scaffolds in bioinorganic or medicinal chemistry research. The presence of the pyridine nitrogen can further influence electronic distribution in the molecule, affecting binding affinities and physicochemical properties such as basicity and solubility.

Overall, 3-(Benzyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine is an efficient intermediate used to access functionalized heteroaromatic compounds. Its design, featuring a stable boronic ester and a removable benzyloxy group, provides synthetic chemists with flexibility in constructing complex molecular architectures required in modern chemical synthesis.