Trimethyl borate → 4-Fluoro-1-naphthaleneboronic Acid (contains varying amounts of Anhydride)

Participants

Reaction Conditions

Reaction Steps

A three-necked 250 mL flask fitted with two dropping funnels, magnetic stirring bar, and low-temperature thermometer was charged with 2-bromo-4fluoronaphthalene (10.9 g, 48.3 mmol) under nitrogen. Dry THF (100 mL) was added, and the solution was cooled to −78° C. To this solution was added n-butyllithium (33.2 mL of a 1.6 M solution, 53.1 mmol) dropwise through the first dropping funnel. The solution was stirred at −78° C. for 2 h whereupon trimethyl borate (6.0 g, 57.9 mmol) dissolved in 10 mL of dry THF was added dropwise through the second dropping funnel. The solution was allowed to warm to room temperature overnight. The reaction was quenched with dilute HCl (20%, 70 mL), and the reaction mixture was concentrated at 30° C. to 50% of its original volume by rotary evaporation and poured into H2O. The resulted biphasic solution was extracted with ethyl acetate (2×100 mL). The organic phases solution were washed twice with H2O and concentrated by rotary evaporation. The crude 4-fluoronaphthalen-1-ylboronic acid product was collected as a white solid powder by filtration and washed with hexane several times to remove impurity. It was dried at 20° C. under vacuum and used without further purification. It gave a white solid product in 78% yield (7.04 g, 37.7 mmol).

Provenance & Evidence