- Voriconazole synthesis method
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The invention relates to a voriconazole synthesis method, which comprises: 1, carrying out catalytic hydrogenation on an SM, anhydrous methanol and anhydrous sodium acetate reaction system by using palladium carbon; after treatment, crystallization is performed to obtain a voriconazole racemate; 2, the voriconazole racemate, an acetone solvent and an L(-)-camphor-10-sulfonic acid system are subjected to a reflux reaction, crystallization and filtration are performed after the reaction is completed, voriconazole camphorsulfonate is obtained, and the molar ratio of L-camphorsulfonic acid to thevoriconazole racemate is 0.5:1; and 3, adjusting the pH value of the voriconazole camphor sulfonate, dichloromethane and water system to 10-11 by using a sodium hydroxide aqueous solution, layering, and temporarily storing an organic phase; extracting the water phase with dichloromethane; and merging the organic phases, carrying out reduced pressure distillation to remove the solvent, and carryingout post-treatment to obtain voriconazole.
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Paragraph 0011; 0048; 0064-0075
(2020/08/02)
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- PROCESS FOR PREPARING VORICONAZOLE BY USING NEW INTERMEDIATES
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Provided is a process for preparing Voriconazole represented by Chemical Formula 1. More particularly, the process for preparing Voriconazole of Chemical Formula 1 includes: carrying out the Reformatsky-type coupling reaction between a ketone derivative of Chemical Formula 4 and a pyrimidine derivative of Chemical Formula 5 to obtain a compound of Chemical Formula 3; reacting the substituents halo and oxysulfonyl with a hydrogen donor to obtain racemicVoriconazole of Chemical Formula 2; and carrying out optical isolation of the racemicVoriconazole by adding an adequate optically active acid thereto to obtain Voriconazole having high optical purity with high cost-efficiency and high yield.
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Page/Page column 14
(2011/09/14)
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- PROCESS FOR THE PREPARATION OF VORICONAZOLE
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The present invention provides a process for preparation of racemic voriconazole in a single reaction vessel. The present invention also provides a process for preparation of voriconazole using racemic voriconazole and the process of making it therewith.
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- PROCESS FOR THE PREPARATION OF VORICONAZOLE
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The present invention relates to an improved process for the preparation of Voriconazole.
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Page/Page column 5
(2010/04/23)
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- PROCESS FOR PREPARATION OF NOVEL SALT OF VORICONAZOLE OXALATE FORM-C
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The invention relates to the process of obtaining novel polymorphic form of voriconazole. Voriconozole has the chemical name (2R, 3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2-4-triazol-yl)-butan-2-ol represented as Formula (1).
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Page/Page column 5
(2009/05/30)
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- IMPROVED PROCESS FOR THE PREPARATION OF (2R,3S)-2-(2,4- DIFLUQROPHENYL)-3-(5-FLUOROPYRIMIDIN-4-YL)-1-(1H-1,2,4-TRIAZOL-1-YL) BUTAN-2-OL
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The present invention is directed to an improved industrially viable, cost effective process to manufacture substantially pure form of (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol (Voriconazole) with a chiral purity level of greater than 99.9% and impurity level of less than 0.1%.
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Page/Page column 8; 12-13
(2009/08/14)
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- PROCESS FOR PREPARING VORICONAZOLE, NEW POLYMORPHIC FORM OF INTERMEDIATE THEREOF, AND USES THEREOF
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The present invention relates to an improved process for preparation of Voriconazole and Voriconazole (1R)-(?)-10-camphorsulfonate.
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Page/Page column 11
(2009/02/11)
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- Process development of voriconazole: A novel broad-spectrum triazole antifungal agent
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In the synthesis of (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1H-1,2,4-triazol-1- yl)-2-butanol (voriconazole), the relative stereochemistry is set in the addition of a 4-(1-metalloethyl)-5-fluoropyrimidine derivative to 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)-1-ethanone. The diastereo-control of this reaction has been examined by variation of pyrimidine substitution pattern and by changes in the metalation and reaction conditions. Excellent diastereoselection (12: 1) is obtained using an organozinc derivative of 6-(1-bromoethyl)-4-chloro-5-fluoropyrimidine. After removal of the chlorine from the pyrimidine ring, the absolute stereochemistry of voriconazole is established via a diastereomeric salt resolution process using (1R)-10-camphorsulfonic acid. Synthetic routes to the pyrimidine partner have also been evaluated. The initial six-step development route from 5-fluorouracil has been superseded by a four-step synthesis involving fluorination of methyl 3-oxopentanoate and cyclisation with formamidine acetate.
- Butters, Mike,Ebbs, Julie,Green, Stuart P.,MacRae, Julie,Morland, Matthew C.,Murtiashaw, Charles W.,Pettman, Alan J.
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