Methanol → Methyl 5-bromo-2-iodobenzoate

Participants

Reaction Conditions

Reaction Steps

Add 5-bromo-2-iodobenzoic acid (1998 g, 6.11 mol) portion wise to a 20° C. solution of sulfuric acid (100 mL) in methanol (13 L). Heat the suspension to reflux for 24 hours, then cool to 20° C. and remove the solvent under reduced pressure. Pour the residue into a 1:1 mixture of methyl-tert-butyl ether and ice water (20 L) and separate the phases. Extract the aqueous phase with methyl-tert-butyl ether (1.5 L), combine the organic phases and wash with aqueous 0.2 M NaOH (5 L), wash with saturated aqueous sodium chloride, dry over sodium sulfate, filter, and evaporate under reduced pressure. Dissolve the crude product in 40-45° C. petroleum ether (10 L), filter through a pad of diatomaceous earth and evaporate under reduced pressure. Dissolve the residue in petroleum ether (5 L) and cool to −50° C., filter the first crop solids, wash the solid with ice cold petroleum ether. Evaporate the mother liquor, redissolve the solid in petroleum ether (1 L), cool to −50° C., and filter a second crop. Combine first and second crops and dry in open air to provide the title compound as a yellow solid (1880 g, 90%).

Provenance & Evidence