Potential GABA_B Receptor Antagonists. II. Synthesis of 1-[2-Amino-1-(4-chlorophenyl)ethyl]-3-oxo-1,3-dihydroisobenzofuran-1-carboxylic Acid

Abstract

Michael addition of methyl 3-oxo-1,3-dihydroisobenzofuran-1-carboxylate to nitrostyrenes is catalysed by amine bases. In non-polar solvents, the use of both enantiomers of ψ-ephedrine as base (0.1 equiv.) leads to both enantiomers , respectively, of a single diastereoisomer. When the reaction mixture is heated, the reaction is neither diastereoselective nor enantioselective. The products have been converted into the potential GABA_B analogue 1-[2-amino-1-(4-chlorophenyl )ethyl]-3-oxo-1,3-dihydroisobenzofuran-1-carboxylic acid.