Trifluoromethanesulfonic acid → 5-Bromo-2-chloro-4-hydroxybenzonitrile

To a solution of 2-chloro-4-hydroxybenzonitrile (10.0 g, 65.11 mmol, Apollo Scientific) in MeCN (200 mL) was added triflic acid (6.32 mL, 71.62 mmol, Spectrochem) and NBS (13.90 g, 78.13 mmol, Spectrochem) at −30° C. The reaction mixture was allowed to warm to RT and stirred for 15 h. The reaction mixture was quenched with saturated aqueous NaHSO3 solution (500 mL) and extracted with ethyl acetate (2×1000 mL). The combined organic layers were washed with water (500 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude compound which was purified by column chromatography (silica gel 100-200 mesh and 0-6% EtOAc in hexane) to obtain 5-bromo-2-chloro-4-hydroxybenzonitrile (7.0 g, 46.2%) as white solid. m/z (ESI) 230.0 (M−H)+.

1. customThe reaction mixture was quenched with saturated aqueous NaHSO3 solution (500 mL)
2. extractionextracted with ethyl acetate (2×1000 mL)
3. washThe combined organic layers were washed with water (500 mL)
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customto obtain the crude compound which
8. customwas purified by column chromatography (silica gel 100-200 mesh and 0-6% EtOAc in hexane)

ORD record

ord-7f717cc535dc4bc2aa39f468cd528447

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012443B2