Hydrogen Peroxide → 8-Fluoro-2,3-dihydro-1,4-benzodioxin-6-ol

温度

-78 °C

To a solution of 7-bromo-5-fluoro-2,3-dihydrobenzo[b][1,4]dioxine (15.1 g, 64.8 mmol) in tetrahydrofuran (160 mL) at −78° C. was added a 1.6 M solution of n-butyllithium in hexanes (45 mL, 73 mmol). The reaction mixture was stirred at −78° C. for 15 min and trimethyl borate (8.5 g, 82 mmol) was added. The reaction mixture was allowed to warm to ambient temperature, stirred for 48 h and cooled to 5° C. 35% w/w aqueous hydrogen peroxide (12.6 mL, 129.6 mmol) was added, the reaction mixture was allowed to warm to ambient temperature and stirred for 3 h. The reaction mixture was diluted with ethyl acetate (200 mL) and the organic phase was washed with 1 M hydrochloric acid (50 mL) and brine (50 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification of the residue by column chromatography eluted with a 0% to 70% gradient of ethyl acetate in hexanes afforded 8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-ol (6.5 g, 59%) as a colorless solid: MS (ES+) m/z 153.0 (M−17).

1. temperatureto warm to ambient temperature
2. stirringstirred for 48 h
3. temperaturecooled to 5° C
4. temperatureto warm to ambient temperature
5. stirringstirred for 3 h
6. washthe organic phase was washed with 1 M hydrochloric acid (50 mL) and brine (50 mL)
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customPurification of the residue by column chromatography
11. washeluted with a 0% to 70% gradient of ethyl acetate in hexanes

ORDレコード

ord-9cf4629eac944d5dbcc87c2871c9551c

出典データセット

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08415370B2