合成路线1

The ethyl ester (III), a chiral key intermediate of this synthesis, can be obtained as follows: 2) The treatment of (trimethylsilyl)acetylene (XII) with butyllithium and NMM in methyl tert-butyl ether (MTBE), followed by hydrolysis with aqueous HCl, gives 3-(trimethylsilyl)-2-propynal (XIII). Treatment of (XIII) with lithium bis(trimethylsilyl)amide (LiHMDS) and trimethylsilyl chloride at -20 C gives the imine (XIV), which is reacted in situ with lithium tert-butyl acetate followed by hydrolysis with aqueous NH4Cl to afford racemic tert-butyl ester (XV). Treatment of (XV) with refluxing ethanol in the presence of p-toluenesulfonic acid gives the corresponding ethyl ester (VII) (already obtained in the preceding scheme). Desilylation of (VII) with NaOEt/EtOH affords racemic 3-amino-4-pentynoic acid ethyl ester in situ, which is then resolved using R-(-)-mandelic acid in ethyl acetate/MTBE to give mandelic acid salt (XVI). Recrystallization of (XVI) from acetonitrile/MTBE and treatment with gaseous HCl in MTBE affords ethyl ester (III) as the hydrochloride.