Regioselective synthesis of ibuprofen via the palladium complex catalyzed hydrocarboxylation of 1-(4-isobutylphenyl)ethanol

Abstract

The synthesis of 2-(4-isobutylphenyl) propionic acid (ibuprofen) by the hydrocarboxylation of 1-(4-isobutylphenyl) ethanol with carbon monoxide and water has been studied in the presence of PdCl2-PPh3-HCl catalyst system. An almost regiospecific synthesis has been achieved under moderate reaction temperatures and pressures. In this reaction system, the liquid phases comprised of an acid-stable organic solvent and an acidic aqueous phase, and the miscibility between two phases were important for efficient hydrocarboxylation. The rate of reaction and the selectivity to the desired branched acid depended strongly upon the pressure of carbon monoxide, the ratio of phosphine ligand to palladium, the concentration of hydrochloric acid, and the nature of halide ion used. (C) 1999 Elsevier Science B.V. All rights reserved.