Methylparaben → Methyl 3-bromo-4-hydroxybenzoate

Participants

Reaction Steps

To a solution of 4-hydroxy-benzoic acid methyl ester (10.0 g, 65.7 mmol) in acetonitrile (110 mL), which has been cooled to at least −5° C. using an ice/acetone bath under a nitrogen atmosphere, was slowly added tetrafluoroboric acid (54% by wt. in diethyl ether, 6.35 g, 72.3 mmol) while maintaining the temperature less than −5° C. After complete addition, a solution of N-bromosuccinimide (12.9 g, 72.3 mmol) dissolved in acetonitrile (55 mL) was slowly added to the reaction mixture such that the temperature did not rise above 10° C. The ice bath was then removed and the reaction mixture was allowed to warm to room temperature and stir for 3 hours. The reaction was quenched by the addition of saturated sodium bisulfite solution until the yellow color was gone. The reaction mixture was extracted with two portions of diethyl ether. The combined organics were washed with one portion of brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography through silica gel using methylene chloride/hexanes (gradient from 80/20 to 100/0) to give 3-bromo-4-hydroxy-benzoic acid methyl ester (13.5 g, 89%) as a white powder. 1H NMR (400 MHz, CDCl3); δ 8.18 (s, 1H), 7.91 (d, 1H), 7.04 (d, 1H), 6.02 (bs, 1H), 3.88 (s, 3H).

Provenance & Evidence