Peracetic Acid → 3-Chloro-5-fluorophenol

Temperature

-78 °C

To a solution of 1-bromo-3-chloro-5-fluorobenzene (16 g, 76 mmol) in 250 mL of anhydrous ether at −78° C. was added tert-butyllithium (1.7 M, 100 mL, 170 mmol). After stirring at −78° C. for 1 h, trimethyl borate (20 mL, 176 mmol) was added, and the reaction was allowed to warm to room temperature overnight. The resulting mixture was cooled to −10° C., and was added peracetic acid (32% in acetic acid, 35 mL). After stirring at 0° C. for 30 min, potassium bisulfite (5 g) was added. After stirring at room temperature for 30 min, the aqueous layer was separated and the organic mixture was extracted with 3 M aqueous sodium hydroxide (3×100 mL). The aqueous extracts were acidified with concentrated hydrochloric acid (pH=2), and was extracted with ether (3×150 mL). The combined ether extracts were dried over anhydrous magnesium sulfate, filtered and concentrated to afford the crude phenol, which was azeotroped with heptane (100 mL) to remove traces of acetic acid to give the title compound. 1H NMR (500 MHz, CD3OD): δ 7.51 (br s, 1H), 7.35 (br d, 1H), 7.21 (m, 1H).

1. temperatureto warm to room temperature overnight
2. temperatureThe resulting mixture was cooled to −10° C.
3. stirringAfter stirring at 0° C. for 30 min
4. stirringAfter stirring at room temperature for 30 min
5. customthe aqueous layer was separated
6. extractionthe organic mixture was extracted with 3 M aqueous sodium hydroxide (3×100 mL)
7. extractionwas extracted with ether (3×150 mL)
8. dry with materialThe combined ether extracts were dried over anhydrous magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customto afford the crude phenol, which
12. customwas azeotroped with heptane (100 mL)
13. customto remove traces of acetic acid

ORD record

ord-efc1919fe17c4eb78ef272990ff72311

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07576239B2