Hydrogen Peroxide → 5-Ethoxy-2-fluorophenol

Temperature

-78 °C

A solution of 56.3 g 4-ethoxy-fluorophenol in 200 ml THF was treated with 84.0 ml pentamethyl-diethylentriamine, cooled to −78° C., then slowly treated with 251 ml 1.6 M n-butyllithium solution in hexane. The reaction mixture was stirred at −78° C. for 3 hrs and then slowly treated with 89.7 ml trimethyl borate. After stirring for 15 min at −78° C., the solution was warmed up to r.t., stirred for an additional 2 hrs and cooled to 0° C. To the mixture were then added dropwise 63.2 ml acetic acid. After stirring for 30 min, 68.3 ml 30% aqueous hydrogen peroxide solution were added slowly. The reaction mixture was warmed up to r.t., stirred overnight and subsequently treated with 200 ml saturated sodium sulfite solution. The mixture was diluted with water and extracted with hexanes. The organic layer was washed with water and brine, dried over MgSO4, filtrated and concentrated to give 60.3 g 5-ethoxy-2-fluoro-phenol as a light brown liquid which was used for the next step without further purification.

1. stirringAfter stirring for 15 min at −78° C.
2. temperaturethe solution was warmed up to r.t.
3. stirringstirred for an additional 2 hrs
4. temperaturecooled to 0° C
5. stirringAfter stirring for 30 min
6. temperatureThe reaction mixture was warmed up to r.t.
7. stirringstirred overnight
8. extractionextracted with hexanes
9. washThe organic layer was washed with water and brine
10. dry with materialdried over MgSO4
11. filtrationfiltrated
12. concentrationconcentrated

ORD record

ord-8e35e8360ecb49589fb06186c4c741ec

Source dataset

uspto-grants-2003_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06642386B2