Syntheses of the (±)‐, (+)‐, and (−)‐Forms of 2‐Amino‐3‐(8‐hydroxyquinolin‐3‐yl)propanoic Acid (8HQ‐3Ala) from a Common Dehydroamino Acid Methyl Ester Precursor

Abstract

AbstractThe (±)‐, (+)‐ and (−)‐forms of 2‐amino‐3‐(8‐hydroxyquinolin‐3‐yl)‐propanoic acid (1 or 8HQ‐3Ala) have been prepared from o‐methoxyacetanilide (2). A combination of Vilsmeier‐Haack, Erlenmeyer‐Plöchl and methanolysis reactions was used to convert compound 2 into the Z‐configured dehydroamino acid derivative 5. Catalytic hydrogenation of the latter compound then gave, after reductive dechlorination and demethylation steps, compound (±)‐1. Asymmetric hydrogenation of compound 5 using a rhodium precatalyst and an enantiopure DuPhos‐type ligand selectively delivered either acid (+)‐1 or (−)‐1. The structure, including absolute configuration, of the latter product was confirmed through single‐crystal X‐ray analysis of the corresponding HBr mono salt.