Iodine → Ethyl 3-bromo-4-hydroxy-5-iodobenzoate

Participants

Reaction Conditions

Reaction Steps

To a mixture of 3-bromo-4-hydroxybenzoic acid ethyl ester (69.2 g, 282 mmol) in 2N aqueous potassium carbonate (423 mL) was added sufficient THF to completely dissolve the phenol and make the solution clear (˜300 to 500 mL). The solution was cooled to 0° C. and I2 (158 g, 621 mmol) was added portionwise at such a rate as not to accumulate a large amount of solid 12 on the bottom of the flask. After addition was complete, the ice bath was removed, and the solution was allowed to warm to room temperature. The reaction was complete in 2 h. Worked up by adding (slowly with caution) solid sodium bisulfite at a rate so excess foaming doesn't occur. Sodium bisulfite was added until nearly decolorized. The mixture was acidified with concentrated hydrochloric acid, extracted several times with ethyl acetate, the organic layers combined, washed with brine, dried over anhydrous sodium sulfate, decanted, and concentrated in vacuo to give 3-bromo-4-hydroxy-5-iodobenzoic acid ethyl ester (94.6 g, 90%) as a pale yellow solid. NMR indicated it was suitable for use in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ1.39 (t, J=6.8 Hz, 3H, —CO2CH2CH3), 4.32 (t, J=6.8 Hz, 2H, —CO2CH2CH3), 8.14 (d, 1H, arom), 8.32 (d, 1H, arom).

Provenance & Evidence