Ethylene Glycol → 3-Bromo-4-(2-hydroxyethoxy)-5-iodobenzoic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

To a mixture of 3-bromo-4-hydroxy-5-iodobenzoic acid ethyl ester (94.6 g, 255 mmol) in 1 L of dry THF was added ethylene glycol (63.2 mL, 1.02 mol) and triphenylphosphine (87 g, 322 mmol). The solution was cooled to 0° C. and diisopropyl azodicarboxylate (60.2 mL, 306 mmol) was added dropwise with stirring. After addition was complete, the ice bath was removed, and the solution was allowed to warm to room temperature. The reaction was complete after 3 h. Worked up by removing ˜½ of the THF via concentration in vacuo, adding water, and extracting with ethyl acetate several times. The organic layers were combined, washed with saturated brine, dried over anhydrous Na2SO4, decanted, and concentrated in vacuo to give a viscous oil which solidified on standing. The major portion of the solid byproducts were removed by stirring with 50% ethyl acetate/hexane. The solid byproduct was filtered off and the liquid was concentrated in vacuo to give a solid which was further purified. Flash chromatography eluting with 5–15% ethyl acetate hexane gave pure 3-bromo-4-(2-hydroxyethoxy)-5-iodobenzoic acid ethyl ester (65 g, 62%). 1H NMR (300 MHz, CDCl3) δ 1.37 (t, J=6.5 Hz, 3H, —CO2CH2CH3), 3.95 (t, J=5 Hz, 2H, —OCH2CH2OH), 4.19 (t, J=5 Hz, 2H, —OCH2CH2OH), 4.32 (t, J=6.5 Hz, 2H, —CO2CH2CH3), 8.18 (d, 1H, arom), 8.37 (d, 1H, arom).

Provenance & Evidence