Sodium Sulfite → 1-Bromo-4-fluoro-5-isopropyl-2-methoxybenzene

Temperature

35 °C

2-fluoro-1-isopropyl-4-methoxybenzene (compound of formula 3, Scheme 3) (34.3 g, 0.204 mol) was dissolved in acetonitrile (400 mL). The solution was warmed to 35° C., and NBS (40 g, 0.225 mol) was added in a single solid addition. The reaction was maintained at 35° C. and was completed in 3-4 hours. The reaction was quenched with 2M Na2SO3 (40 mL, 0.08 mol). The resulting mixture was concentrated to ¼ of the total volume and diluted with water (400 mL) and petroleum ether (300 mL). The organic layer was cut and washed with water (300 mL), dried over Na2SO4 and filtered. The solvent was removed under reduced pressure to yield 1-bromo-4-fluoro-5-isopropyl-2-methoxybenzene (compound of formula 4, Scheme 3) as a slightly yellow oil (49.26 g, 98%). 1H NMR (CDCl3) δ 1.22 (d, J=6.9 Hz, 6H), 3.14 (sept., J=6.9 Hz, 1H), 3.85 (s, 3H), 6.60 (d, J=11.8 Hz, 1H), 7.37 (d, J=8.0 Hz, 1H).

1. temperatureThe reaction was maintained at 35° C.
2. concentrationThe resulting mixture was concentrated
3. additiondiluted with water (400 mL) and petroleum ether (300 mL)
4. washwashed with water (300 mL)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. customThe solvent was removed under reduced pressure

ORD record

ord-7d7bba4911d84c37851eecf64e605457

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09212118B2