2-METHYL-3-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-YL)PHEN

2-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol is widely employed in the synthesis of pharmaceutical intermediates where a hydroxyl‑bearing biaryl is required. The phenol group of 2-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol can be selectively alkylated under mild basic conditions without affecting the boronate ester, enabling sequential functionalization. In drug discovery, 2-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol is used to prepare estrogen receptor modulators, antibacterial biaryls, and kinase inhibitors with a 3‑hydroxyphenyl motif. Cosperpharm’s manufacturing ensures that 2-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol is supplied with a well‑controlled regioisomeric purity, as the 4‑boronate‑2‑methylphenol isomer must be minimized to prevent isomeric contamination in the final coupling product.

Product Parameters

Product Advantages

1. Two Reactive Sites, One Molecule – The boronate ester and free phenol can be addressed independently, saving two synthetic steps.

2. Regiochemically Defined – The boronate is exclusively at the 3‑position relative to the phenol, confirmed by NOE or X‑ray analysis.

3. Electron‑Rich Ring – The methyl and hydroxyl groups activate the ring for electrophilic substitution after coupling.

4. Stable Crystalline Solid – Unlike many phenol‑boronates that are oils, this compound is a well‑behaved solid.

5. Scalable Supply – Cosperpharm supplies this boronate from 1‑g to 10‑kg lots, with batch records suitable for regulatory filings.

Synthetic Route

2-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol is prepared by the Miyaura borylation of 3‑bromo‑2‑methylphenol with bis(pinacolato)diboron, using Pd(dppf)Cl₂ and potassium acetate in anhydrous dioxane at 80–100 °C. The reaction is monitored by HPLC for complete consumption of the bromide. After workup, the product is purified by column chromatography or recrystallization.

FAQ

Q1: Can the phenol be alkylated without affecting the boronate?

A: Yes, Williamson ether synthesis (alkyl halide, K₂CO₃, DMF) proceeds cleanly at the phenol. The boronate remains intact under these neutral or mildly basic conditions.

Q2: What is the recommended Suzuki coupling procedure?

A: Use 1.1 equiv of this boronate, 1.0 equiv of aryl bromide, Pd(PPh₃)₄ (2 mol%), and 2 M K₂CO₃ in DME/water at 85 °C. The free phenol does not interfere.

Contact Us

To evaluate this phenol‑substituted boronate ester in your next Suzuki‑driven library, reach out to Cosperpharm’s technical sales department — we’ll arrange for a free sample and share a detailed coupling report to jumpstart your work.