Hydrochloric Acid → 3-Bromo-5-fluorophenol

Participants

Reaction Conditions

Reaction Steps

To a N2 flushed, 2 L four necked flask equipped with a mechanical stirrer, a condenser, a temperature controller and a N2 inlet, was added potassium trimethylsilanolate (225.0 g, 1.75 mol, tech. purify 90%), 1-bromo-3,5-difluorobenzene (96.5 g, 0.5 mol) and diglyme (300 mL). The reaction mixture was heated to 120° C. under N2 for 5 h. After cooling to rt, the heating mantle was replaced with an ice bath. The reaction mixture was acidified with a 3 N HCl solution (600 mL) while keeping the reaction temperature below 30° C. Tertiary butyl methyl ether (1 L) was added and the resulting mixture was stirred below 20° C. for 30 min then transferred to a 5 L separatory funnel. The organic layer was separated and washed with water (3×500 mL), sat. NaCl (500 mL), dried over MgSO4, filtered and concentrated in vacuo to give the crude red solid (145.0 g). The crude material was then distillated at 52-55° C./0.1 mm Hg to yield 3-bromo-5-fluorophenol as a slightly yellow oil (88.0 g, 92% yield). 1H NMR (300 MHz, CDCl3) δ 5.34 (s, H), 6.47-6.52 (m, 1H), 6.77-6.83 (m, 2H).

Provenance & Evidence