Hydrogen Peroxide → 2-Fluoro-5-methoxyphenol

Participants

Reaction Conditions

Reaction Steps

To a flask, 4-fluoroanisole (20.00 g, 159 mmol), N,N,N′,N″,N″-pentamethyldiethylenetriamine (27.75 g, 160 mmol), and tetrahydrofuran (100 mL) were added, and the resulting mixture was cooled to −70° C. under nitrogen atmosphere. To the solution, n-butyllithium (59.2 mL, 163 mmol, 2.76 M, in hexane) was added dropwise, and trimethyl borate (39.8 mL, 357 mmol) was added three hours later. One hour later, the reaction mixture was warmed to −10° C., and acetic acid (28.0 mL) was added thereto. The reaction temperature was then changed to 5° C., and 30% aqueous hydrogen peroxide solution (30 mL) was added dropwise to the reaction mixture, after which the resulting mixture was stirred overnight at room temperature. To the reaction mixture, 10% aqueous sodium sulfite solution was added, and the resulting mixture was extracted with tert-butyl methyl ether. To the organic layer, a 2 N aqueous sodium hydroxide solution was added, and the resulting mixture was extracted. After adding 5 N hydrochloric acid to the aqueous layer to adjust the pH to 6, the resulting mixture was extracted with tert-butyl methyl ether. The organic layer was sequentially washed with water and 5% saline, dried over anhydrous magnesium sulfate, and then filtered. The filtrate obtained was concentrated under reduced pressure to obtain the captioned compound (21.7 g) as a colorless oil.

Provenance & Evidence