960067-33-8

2-Difluoromethoxyphenylboronic Acid, Pinacol Ester is an intermediate in preparation of pyridine derivatives as voltage-gated sodium channel modulators useful in the treatment of pain.

The general procedure for the synthesis of 2-difluoromethoxyphenylboronic acid pinacol ester from o-bromodifluoromethoxybenzene and bis(pinacolato)diboron (1.71 g, 6.75 mmol) was carried out as follows: o-bromodifluoromethoxybenzene (1 g, 4.5 mmol) and bis(pinacolato)diboron (1.71 g, 6.75 mmol) were dissolved in dioxane (10 mL), and followed by addition of anhydrous potassium acetate (1.1 g, 13.53 mmol ) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (369 mg, 0.45 mmol). The reaction mixture was heated to 85 °C under nitrogen protection and stirred continuously for 16 hours. Upon completion of the reaction, the mixture was cooled to room temperature and subsequently concentrated under reduced pressure. The residue was purified by silica gel column chromatography with an eluent ratio of petroleum ether: ethyl acetate = 10:1, resulting in the light yellow oily product 2-difluoromethoxyphenylboronic acid pinacol ester (1.1 g, 90.2% yield).

[1] Patent: US2018/208604, 2018, A1. Location in patent: Paragraph 0216-0217
[2] Patent: WO2008/135826, 2008, A2. Location in patent: Page/Page column 156; 157