Acetic Acid → 2-Fluoro-3-methoxyphenol

Temperature

-78 °C

A mixture of 2-fluoroanisole (1.8 ml, 15.85 mmol), pentamethyldiethyenetriamine (3.6 mL, 17.45 mmol) and tetrahydrofuran (10 mL) is stirred at −78° C. A 2.5 M solution of n-butyllithium in hexanes (7 ml, 17.45 mmol) is added dropwise and the resulting solution is stirred at −78° C. 2 hr. Trimethylborate (2 mL, 17.45 mmol) is added and the reaction is warmed to room temperature and stirred 1 hr. Acetic acid (1.4 ml, 23.8 mmol) is added followed by an aqueous 30% solution of hydrogen peroxide (1.8 mL, 17.45 mmol) and the resulting mixture is stirred rapidly 18 hr at room temperature. The reaction mixture is diluted with water 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 purified via silica chromatography eluting with hexanes to 8:1 hexanes:ethyl acetate to give the title compound (1.65 g, 73%) as a colorless oil. MS ES 141 M−1.

1. stirringthe resulting solution is stirred at −78° C
2. custom2 hr
3. temperaturethe reaction is warmed to room temperature
4. stirringstirred 1 hr
5. stirringthe resulting mixture is stirred rapidly 18 hr at room temperature
6. extractionextracted with ethyl acetate (3×50 mL)
7. dry with materialThe combined extracts are dried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated to about 10 mL volume
10. customThe resulting mixture is purified via silica chromatography
11. washeluting with hexanes to 8:1 hexanes

ORD record

ord-49d7a883375d4d4ab09fbf25293a871a

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07598423B2