168828-89-5Relevant articles and documents
Linezolid preparation method
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Paragraph 0019, (2019/02/03)
The invention relates to a linezolid preparation method. 3-fluoro-4-morpholinyl aniline is taken as a starting material and subjected to a reaction with (S)-(+)-N-(2,3-ethoxypropyl) phthalimide, an intermediate 1 is generated and subjected to a cyclization reaction with a carbonylation agent, an intermediate 2 is generated, an ammonolysis reaction and an acetylation reaction are performed, and a target compound is obtained. The problems of poor safety, strict conditions, many impurities and low yield, which are not suitable for industrial production, of a linezolid preparation method in the prior art are solved, the starting material of the route is cheap and available, the operation is simple, hazardous reagents are avoided, the solvent is easily recycled and reused, reaction yield is higher, purity of a final product is up to 99.9% or higher, and the linezolid preparation method is suitable for industrial production.
A novel method for preparation of linezolid, (S)-N-((3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl) methyl) acetamide
Seku, Kondaiah,Badathala, Vijayakumar,RaoVelivelad, Venkata Srinivasa,Desireddy, Srinivasa Reddy
, p. 56 - 60 (2017/03/08)
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 C16H20FN3O4and 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.
Process for the preparation of linezolid
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Page/Page column 17, (2017/05/31)
The present invention relates to an improved process for the preparation of Linezolid. More specifically, the present invention relates to an improved process for preparing (S)—N-[[3-[3-fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl] phthalimide and (S)-glycidyl phthalimide intermediates, which are used in the preparation of Linezolid.