570391-20-7

3-Bromo-5-iodophenol is a reactant in the preparation of N-[3-(1H-Indol-4-yl)-5-(2-methoxyisonicotinoyl)phenyl]methanesulfonamide (LP-261), a potent antimitotic agent.

General procedure for the synthesis of 3-bromo-5-iodophenol from 1-bromo-3-iodo-5-methoxybenzene: 1-bromo-3-iodo-5-methoxybenzene (6.29 g, 20.1 mmol) was suspended in a 33% hydrogen bromide solution in acetic acid (150 mL). Tetrabutylammonium bromide (0.5 g, 1.55 mmol) was added and the mixture was heated to reflux with vigorous stirring and the reaction continued for 2 days. After completion of the reaction, the mixture was cooled to room temperature and extracted with dichloromethane (3 × 100 mL). The organic layers were combined, washed with water (50 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give the crude product. The crude product was purified by rapid chromatography on silica gel (300 g of silica gel, eluent ethyl acetate/heptane 1:9) to afford 3-bromo-5-iodophenol (21.2 g, 96% yield) as a light brown solid.

[1] Patent: US2006/270686, 2006, A1. Location in patent: Page/Page column 41
[2] Patent: US2008/280891, 2008, A1. Location in patent: Page/Page column 41
[3] Patent: WO2008/8059, 2008, A1. Location in patent: Page/Page column 117