- General Synthesis of Industrial Cephalosporin-Based Antibiotics Through Amidation with Tosyl Chloride as a Coupling Reagent
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In this contribution we demonstrate the feasibility of a recently developed amidation method for a general synthesis of industrially important semi-synthetic cephalosporin antibiotics starting from readily available 7-aminocephalosporanic acid and derivatives thereof. The amidation process is based on the use of 4-toluene-sulfonyl chloride as an economically attractive coupling reagent in combination with methanol or ethyl acetate as one of the solvent components. A broad reaction scope was shown by the successful synthesis of three further cephalosporin antibiotics with different functionalities, which were obtained in high yields of 82–95 % in the reactions even under non-optimized conditions. It is noteworthy that also different oxime functionalities in the side chain of the 7′-position are tolerated as well as an ester moiety in 4′-position and a cationic functionality in 3′-position. Thus, this amidation process through an activated anhydride formed by means of 4-toluenesulfonyl chloride is a broadly applicable methodology for the synthesis of industrial semi-synthetic cephalosporin antibiotics.
- Pieper, Matthias,Schleich, Herbert,Gr?ger, Harald
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- Technical method for reducing ceftazidime impurity H
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The invention provides a technical method for reducing a ceftazidime impurity H. The technical method is characterized in that one or more of dichloromethane, trichloromethane, carbon tetrachloride, tetrahydrofuran, acetonitrile and 2-methyltetrahydrofuran as a main solvent, tert-butyl alcohol or a mixed solvent of tert butyl alcohol and methyl alcohol is taken as a cosolvent, 7-APCA and BPTA aresubjected to a condensation reaction under the alkaline condition, ceftazidime tert-butyl ester is generated and subjected to water treatment, solvent crystallization is performed, and ceftazidime isobtained. Content of the impurity ceftazidime methyl ester (H) obtained with method in the product is smaller than 0.1%, and unknown impurities can be controlled to be 0.05% or smaller.
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Paragraph 0041-0043; 0050-0052; 0059-0061
(2019/07/04)
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- IMPROVED PROCESS FOR THE PREPARATION OF CEPHALOSPORIN ANTIBIOTICS
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Abstract The present invention more particularly relates to a process for the preparation of cephalosporin antibiotics of the Formula (I) wherein R1 represents hydrogen, trityl, alkyl like CH3, CRaRbCOORc where Ra and Rb independently represent hydrogen or methyl and Rc represents hydrogen or (C1-C6) alkyl; R2 is carboxylate ion or COORd, where Rd represents hydrogen, ester or a counter ion which forms a salt; R3 represents hydrogen, CH3, CH2OCH3, CH2OCOCH3, CH=CH2, Formula (II).
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Page/Page column 12-13
(2008/06/13)
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