Background: Linezolid (I) [(S)-N-((3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl)
methyl) acetamide] is a synthetic antibiotic used for the treatment of serious infections caused by grampositive
bacteria that are resistant to other antibiotics. Linezolid empirical formula is C16H20FN3O4 and
its molecular weight is 337.35. It is active against most Gram-positive bacteria that cause disease, including
streptococci, vancomycin-resistant enterococci (VRE), and methicillin-resistant Staphylococcus
aureus (MRSA). The main uses are infections of the skin and pneumonia, although it may be used for a
variety of other infections. Linezolid was discovered in the 1990s by a team at Pharmacia and Upjohn
Company and first approved for use in 2000. Lohray et al., in 1999, have reported a synthetic method
for Linezolid starting from D-mannitol, the chemical synthesis of Linezolid by alternate route has attracted
several research groups in the past 15years.
Methods: An improved and economically viable process is described to prepare Linezolid wherein
methyl 3- fluoro-4- morphinolino phenyl carbamate (V) is reacted with R-epichlorohydrin in the presence
of n-butyllithium in hexane to obtain (R)-5-(chloromethyl)-3-(3-fluoro-4-morpholinophenyl) oxazolidin-
2-one (IV) which reacts with potassium phthalimide in presence of polar solvent to give (S)-2-
[3-(3-3-fluoro-4-morpholin-4-yl-phenyl)-oxazolidine-5-yl methyl]-isoindole-1,3-dione (III), which is
subsequently converted to Linezolid.
Results: Linezolid was obtained via only four steps with yield 90% and high purity. This process avoids
formation and use of sensitive intermediates. It is an improved process for the preparation of an intermediate
(R)-5-(chloromethyl)-3-(3-fluoro-4-morpholinophenyl) oxazolidin-2-one (formula IV).
Conclusion: Linezolid was successfully synthesized from (3-fluoro-4-morpholin-4-yl-phenyl)-carbamic
ester via R-epichlorohydrin and potassium phthalimide and developed new intermediate (5R)-5-chloromethyl
-3-(3-fluoro-4-morpholin-4-yl-phenyl) oxazolidin-2-one (IV). The present method relates to a novel,
cost effective and industrially viable process. Thus, the process described is less cumbersome by way of
reduced reaction stages, high purity and quantity of the yield. In comparison with previously reported
synthetic strategies, this novel approach is believed to be the shortest and the most efficient synthetic
route to date.