Trimethyl borate → 5-Fluoro-2-methoxyphenylboronic acid

A cold solution (−78° C.) of 2-bromo-4-fluoro-anisole (20 g, 10 mmol, 1 equiv) in anhydrous tetrahydrofuran (200 mL) was treated dropwise, over 20 min, with 2.5M n-butyllithium solution in hexanes (44 mL, 110 mmol, 1.1 equiv). The reaction was stirred for 1 hour, then trimethyl borate (16.75 mL, 150 mmol, 1.5 equiv) was added in one portion. After stirring overnight at room temperature, the reaction was poured into saturated ammonium chloride (200 mL). The layers were separated and the aqueous phase was extracted with ethyl acetate (3×200 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The solid residue was triturated with methyl tert-butyl ether (100 mL) to give (5-fluoro-2-methoxyphenyl)boronic acid (1) (6.5 g, 39% yield) as an off-white solid.

1. stirringAfter stirring overnight at room temperature
2. customThe layers were separated
3. extractionthe aqueous phase was extracted with ethyl acetate (3×200 mL)
4. dry with materialThe combined organic layers were dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe solid residue was triturated with methyl tert-butyl ether (100 mL)

ORD record

ord-7e3041d89ce74c2db738138da35d669e

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952114B2