Hydrogen Bromide → 1-Bromo-4-fluoro-5-isopropyl-2-methoxybenzene

Temperature

27.5 °C

The crude 3-fluoro-4-isopropylanisole solution from the previous step (100 ml, 0.82 M, 82 mmol) was stirred at 20° C. in the dark. Aqueous 48 wt % HBr (16.6 g, 98.5 mmol) and aqueous 35 wt % hydrogen peroxide (14.0 g, 144 mmol) were added concomitantly over 40 min. The reaction mixture was maintained at 25-30° C. during the addition. The mixture was stirred at 30° C. for 3 h and then was cooled to 5° C. Sodium sulfite (4.2 g) was added in portions over 30 min while maintaining the quench temperature at <20° C. The aqueous layer was removed, and the organic layer was washed with 2 M KHCO3 (20 ml), concentrated, and flushed with heptane (50 ml) at 30-40° C. under reduced pressure to afford 2-bromo-4-isopropyl-5-fluoroanisole as a pale yellow liquid in 98% yield.

1. temperaturewas cooled to 5° C
2. temperaturewhile maintaining the quench temperature at <20° C
3. customThe aqueous layer was removed
4. washthe organic layer was washed with 2 M KHCO3 (20 ml)
5. concentrationconcentrated
6. customflushed with heptane (50 ml) at 30-40° C. under reduced pressure

ORD record

ord-12db1d71e8f844c3af90d8339f57e0d4

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09145348B2