Hydrogen Bromide → 2,4-Dichloro-5-fluoro-3-methoxybromobenzene

Temperature

2.5 °C

To 165 ml of a mixture of concentrated hydrochloric acid and water (1:1) was added 52.5 g of 2,4-dichloro-5-fluoro-3-methoxyaniline (0.25 mol). The resultant was stirred to be a slurry, and cooled to 0-5° C. Over 30 minutes, a solution of sodium nitrite (18.2 g) in water (50 ml) was added dropwise to the slurry. The resulting solution was added slowly to a solution of cuprous bromide (0.299 mol) and hydrobromic acid (160 ml). The reactant was stirred for 2 hours, and kept overnight. The resulting mixture was wet-distilled and the distilled materials were extracted with toluene. The oil layer was washed with 10% aqueous solution of NaOH, concentric sulfuric acid and water, dried over anhydrous sodium sulfate, and evaporated. The residue was purified by silica gel chromatography eluting with n-hexane-dichloromethane to give 58.1 g of 2,4-dichloro-5-fluoro-3-methoxybromobenzene (0.212 mol) in 84.9% yield.

1. stirringThe reactant was stirred for 2 hours
2. waitkept overnight
3. distillationThe resulting mixture was wet-distilled
4. extractionthe distilled materials were extracted with toluene
5. washThe oil layer was washed with 10% aqueous solution of NaOH, concentric sulfuric acid and water
6. dry with materialdried over anhydrous sodium sulfate
7. customevaporated
8. customThe residue was purified by silica gel chromatography
9. washeluting with n-hexane-dichloromethane

ORD record

ord-6ebdf7c807b44dbeb8159ba343dbd81b

Source dataset

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06699992B2