Synthesis of L-(5-Chloro-2-pyridyl)glycine

A practical synthesis of the new amino acid L-(5-chloro-2-pyridyl)glycine (2) was developed (Scheme I). The reaction sequence was initiated by condensing 2-chloro-5-nitropyridine with diethyl acetamidomalonate to afford diethyl (5-nitro-2-pyridyl)acetamidomalonate (5). Reduction of the 5-nitro group and application of the isoamyl nitrite-carbon tetrachloride reagent provided diethyl (5-chloro-2-pyridyl)acetamidomalonate (8). Selective base hydrolysis followed by enzymatic hydrolysis furnished amino acid 2.