3-Ethoxy-4-iodobenzoic acid ethyl ester synthesis

Yield:741699-04-7 96%

Reaction Conditions:

with potassium carbonate in acetonitrile at 20 - 65;

Steps:

3

Reflux 3-hydroxy-4-iodo-benzoic acid (38 g, 144 mmol) and saturated solution of HCl in ethanol (600 mL) overnight. Evaporate the solvent yielding 42 g, 99% of 3-hydroxy-4-iodo-benzoic acid ethyl ester. ¹H NMR (300 MHz, CDCl₃): δ 1.39 (t, J=7.1 Hz, 3H), 4.36 (q, J=7.1 Hz, 2H), 7.33 (dd, J=8.3 and 2.0 Hz, 1H), 7.64 (d, J=2.0 Hz, 1H), 7.75 (d, J=8.3 Hz, 1H). Add ethyl iodide (33.8 g, 216 mmol) to a solution of 3-hydroxy-4-iodo-benzoic acid ethyl ester (42 g, 144 mmol) and K₂CO₃ (39.9 g, 288 mmol) in acetonitrile (400 mL) under magnetic stirring. Heat the reaction mixture at 65° C. for 2 hours, allow the mixture to cool and maintain at RT overnight. Evaporate the solvent and add ethyl acetate to the crude. Filter the solid through Celite and evaporate the solvent. Yield 42 g, 96%. ¹H NMR (300 MHz, CDCl₃): δ 1.39 (t, J=7.1 Hz, 3H), 1.50 (t, J=7.0 Hz, 3H), 4.16 (q, J=7.0 Hz, 2H), 4.37 (q, J=7.1 Hz, 2H), 7.36 (dd, J=8.1 and 1.8 Hz, 1H), 7.42 (d, J=1.8 Hz, 1H), 7.84 (d, J=8.1 Hz, 1H).

References:

US2006/276532,2006,A1 Location in patent:Page/Page column 5