Hydrochloric Acid → 3-Bromo-5-fluorophenol

Temperature

120 °C

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).

1. customTo a N2 flushed
2. custom2 L four necked flask equipped with a mechanical stirrer, a condenser
3. temperatureAfter cooling to rt
4. customthe heating mantle was replaced with an ice bath
5. customthe reaction temperature below 30° C
6. customthen transferred to a 5 L separatory funnel
7. customThe organic layer was separated
8. washwashed with water (3×500 mL), sat. NaCl (500 mL)
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customto give the crude red solid (145.0 g)
13. customwas then distillated at 52-55° C.

ORD record

ord-292af837dd144235a546d8d5e1311d1f

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08642576B2