Acetic Acid → 1-(3-Fluoro-2,4-dihydroxy-phenyl)-ethanone

Temperature

0 °C

A solution of 2-fluoro-3-methoxy-phenol (0.5 g, 3.53 mmol) and dichloromethane is stirred at −78° C. A 1M solution of boron tribromide in dichloromethane (3.9 mL, 3.9 mmol) is added slowly and the mixture is stirred 10 min cold, then warmed to 0° C. and stirred 1 hr. The reaction is quenched with ice and stirred at room temperature overnight. The product is extracted with ethyl acetate (2×50 mL), dried over magnesium sulfate, filtered, and concentrated. The resulting residue is combined with boron trifluoride diethyl etherate (1.3 mL, 10.3 mmol) and acetic acid (0.2 mL, 3.28 mmol) and heated to reflux 8 hr. The mixture is cooled to room temperature, diluted with water (50 mL), and extracted with ethyl acetate (3×50 mL). The combined extracts are dried over magnesium sulfate, filtered and concentrated to about 10 mL volume. The resulting mixture is diluted with hexanes (50 mL), cooled to 0° C., and filtered to give the title compound (310 mg, 58%) as a tan solid. MS ES 171 M+1.

1. stirringstirred 1 hr
2. customThe reaction is quenched with ice
3. stirringstirred at room temperature overnight
4. extractionThe product is extracted with ethyl acetate (2×50 mL)
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. temperatureheated
9. temperatureto reflux 8 hr
10. temperatureThe mixture is cooled to room temperature
11. extractionextracted with ethyl acetate (3×50 mL)
12. dry with materialThe combined extracts are dried over magnesium sulfate
13. filtrationfiltered
14. concentrationconcentrated to about 10 mL volume
15. additionThe resulting mixture is diluted with hexanes (50 mL)
16. temperaturecooled to 0° C.
17. filtrationfiltered

ORD record

ord-f04b7f5d958947899c40ec61174af811

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07598423B2