Starting with L-glutamic acid-5-methyl ester, it was first reacted with di-tert-butyl dicarbonate in a triethylamine/DMF system at 50°C for 1 hour, then incubated overnight at room temperature. Column chromatography yielded a Boc-protected intermediate. This intermediate was dissolved in THF, reduced at -10°C with N-methylmorpholine, ethyl chloroformate, and sodium borohydride, quenched with saturated ammonium chloride, and purified by extraction to obtain a hydroxyl intermediate. This hydroxyl intermediate was then reacted with p-toluenesulfonyl chloride and triethylamine in dichloromethane at room temperature, and column chromatography yielded a sulfonyloxy intermediate. Subsequently, it was heated with sodium azide in DMF at 50°C for 3 hours to purify an azide intermediate. The azide intermediate was dissolved in methanol and hydrogenated overnight under atmospheric pressure using a 10% palladium/carbon catalyst. The solvent was removed by filtration to obtain a cyclization product. Finally, the cyclization product was dissolved in ethanol, and acetyl chloride was added at 0°C. The mixture was stirred at room temperature for 1 hour, and the solvent was removed under reduced pressure to obtain (S)-5-amino-piperidin-2-one hcl.
