合成路线1

Cyclization of oxoester (I) with aqueous hydroxylamine at 0 C gave a mixture of two isoxazoles (II) and (III), which were separated by column chromatography. Methylation of (II) with ethereal diazomethane provided methyl ether (IV). This was regioselectively brominated with Br2 at 50 C to give bromomethyl compound (V). Further treatment with dimethyl acetamidomalonate (VI) and NaOMe in refluxing methanol gave (VII) (1). Then, hydrolysis and decarboxylation of malonate (VII) in refluxing 2 M HCl afforded racemic amino acid (VIII), and subsequent protection with di-tert-butyl dicarbonate gave carbamate (IX). Formation of the salt with (S)-1-phenylethylamine (X) and recrystallization from EtOH-Et2O provided pure (S)-amino acid as the phenylethylamine salt (XI). Free acid was obtained by treatment with acetic acid, and then a reflux in concentrated HBr effected hydrolysis of both methyl ether and carbamate groups to afford the target (S)-amino acid.