PURPOSE: To readily obtain the titled compound useful as a precursor of a synthetic intermediate for angiotensin converting enzyme (ACE) inhibitors in high yield, by reacting ethyl β-benzoylacrylate with alanine in the presence of an amine.
CONSTITUTION: Ethyl β-benzoylacrylate is reacted with alanine in the presence of an amine to afford ethyl α-(1-carboxyethyl)amino-γ-oxo-γ-phenylbutyrate expressed by formula I. The reaction is preferably carried out by using ethanol, water or a mixture thereof as a solvent and an ion exchange resin having primary amine, secondary amine, tertiary amine or quaternary ammonium groups as exchange groups as the amine. Diastereomers of (αS,1S) isomer are preferentially formed by the above-mentioned addition reaction and the (αS,1S) isomer is selectively deposited as crystals by neutralization with an equivalent amount of an acid after the addition. The crystals are then reduced to afford the aimed compound expressed by formula II which is a synthetic intermediate for angiotensin converting enzyme inhibitors.
YAMADA KAZUHIKO
YAMADA YUKIO
NOMURA MICHIO
OHASHI TAKEHISA
WATANABE KIYOSHI
