A Facile Method for the Production of d -p-Hydroxyphenylglycine. Asymmetric Transformation of Dl -p-Hydroxyphenylglycine Using (+)-1-Phenylethanesulfonic Acid

A practical method for the production of d-p-hydroxyphenylglycine, useful as a starting material for preparing semisynthetic penicillins or cephalosporins, has been developed. The diastereomeric salts of Dl-p-hydroxyphenylglycine with (+)-1-phenylethanesulfonic acid as a resolving agent, were efficiently resolved into less soluble d-p-hydroxyphenylglycine (+)-1-phenylethanesulfonate [d-HPG·(+)-PES] and soluble l-HPG·(+)-PES by the fractional crystallization of its salts in aqueous solution. The soluble l-HPG·(+)-PES could be easily epimerized into Dl-HPG·(+)-PES by heating it with water containing a 0.1 molar equivalent of free Dl-HPG in an autoclave. When the fractional crystallization of Dl-HPG with (+)-PES was simultaneously carried out under the epimerizing conditions, the Dl-HPG·(+)-PES was transformed into d-HPG·(+)-PES in up to 90% yield. The present asymmetric transformation should be a suitable method for preparing d-HPG in a large scale.