Improved Synthesis Of A New Antibacterial Agent-Linezolid

The oxazolidinones is listed after the quinolone antibacterial drugs and a class of total synthesis of new antibacterial drugs.This kind of antimicrobials has unique mechanism of action,novel structure,effective against gram-positive bacteria,and no cross resistance with other antimicrobials.Currently these drugs only listed Linezolid and todizolid.The most important representatives is Linezolid in nearly 10 years,which synthetized by pharmacia upjohn company and first listed in the United States in 2000,after seven years listed in China.This article is mainly to compare the synthesis routes of Linezoild,choose a route suitable for industrial production.The intermediates N-benzyloxycarbonyl-3-Fluoro-4-anisidine and(S)-N-(3-chlorine-2-acetoxypropyl)acetamide was respect-tively synthesized from morpholine,3-fluoro-4-morpholino benzenamine and(S)-Epichlorohydrin.The condensation of two intermediates afford the target compound.We use two routes on the synthesis of(S)-N-(3-chlorine-2-acetoxypropyl)acetamide.Acetylation of(2S)-1-Amino-3-chloro-2-propanol acetate is difference from literature.To make a study of synthesis process which is optimizing for the reaction.By using reversed-phase high performance liquid chromatography detections the reactions.The structures of the key intermediates and the target product were confirmed by the analysis of 1H-NMR and IR data.Finally using high performance liquid chromatography-mass spectrometry(LC-MS)to test the purity of the product.