- Preparation method of cefpodoxime acid
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The invention discloses a preparation method of cefpodoxime acid. The method comprises the following steps: adding a proper amount of solvent, 7-amino-3-chloromethyl cephalosporanic acid as shown in a formula (III), sodium methoxide, a quaternary ammonium salt catalyst and potassium iodide into a reaction container, performing stirring reaction at 0-80 DEG C for 2-8 hours, then adding 2-(2-amino-4-thiazolyl)-2-(Z)-methoxy imino acetyl chloride as shown in a formula (IV), performing stirring reaction at 0-30 DEG C for 2-5 hours, and after the reaction is finished, performing post-treatment to obtain cefpodoxime acid as shown in a formula (II). The method is simple and easy to operate, high in reaction yield, green and environmentally friendly, avoids the use of inflammable and explosive raw materials with high toxicity, improves the purity of the product by the post-treatment process, and is suitable for industrial production.
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Paragraph 0023-0027
(2021/07/31)
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- 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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p. 3259 - 3263
(2019/06/04)
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- A PROCESS FOR ALKYLATING THE HYDROXYMETHYL GROUP AT POSITION -3 OF CEPHALOSPORINS
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A process for alkylating the hydroxymethyl group at position -3 of 7-Amino-3- hydroxymethyl-3-cephem-4-carboxylic acid (D-7-ACA) using an alkylating agent, strong acid and a suitable solvent(s).
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Page/Page column 9
(2017/09/27)
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- Preparation method of cefpodoxime proxetil
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The invention discloses a preparation method of cefpodoxime proxetil. In the method, a compound of formula II is used as an initial raw material, the intermediate compound of formula III is not separated during the process, and a crude product of cefpodoxime proxetil is synthesized by one step; and after that, a simple and easy recrystallization method is adopted for purifying the crude product of cefpodoxime proxetil to obtain cefpodoxime proxetil. In the preparation method disclosed by the invention, the yield is increased without reducing the quality, the obtained product has high purity, the synthesis path is simple, and the preparation method is suitable for industrial production.
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Paragraph 0034; 0036; 0038; 0040
(2017/07/21)
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- Synthesis method of cefpodoxime proxetil intermediate
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The invention discloses a synthesis method of a cefpodoxime proxetil intermediate, namely (6R,7R)-7-[2-(2-amino-4-thiazolyl)-(Z)-2-(methoxyimino)acetamido]-3-methoxymethyl-8-oxo-5-thio-1-azabicyclo[4.2.0]oct-2-ene-2-methanoic acid. The synthesis method includes: enabling chlorosulfonic acid and methanol to react to prepare methoxy sulfonic acid; under the action of the methoxy sulfonic acid and dimethylformamide, etherifying 7-ACA (7-aminocephalosporanic acid) and trimethyl borate prior to aftertreatment, adding into a water and methanol solution reversely to guarantee that the obtained intermediate isn't sticky and is loose, drying and grafting with AE active ester so as to obtain a target product, namely the cefpodoxime proxetil intermediate. The synthesis method of the cefpodoxime proxetil intermediate has the advantages that synthesis steps of 3-position and 7-position protection and desorption of 7-ACA can be omitted, so that low step cost, high yield and high purity are achieved, all materials are cheap and available, and industrial production and little pollution are benefited.
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Paragraph 0010; 0011; 0012
(2016/11/09)
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- AN IMPROVED PROCESS FOR CEFPODOXIME ACID
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The present invention relates to an improved process for the preparation of cefpodoxime acid from 7-Amino cephalosporanic acid. Further the preparation of cefpodoxime proxetil from cefpodoxime acid is also described.
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- AN IMPROVED PROCESS FOR THE PREPARATION OF CEFPODOXIME ACID
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The present invention relates to the preparation of cefpodoxime acid of formula (I) using alcoholic solvent in the presence or absence of water in a very safe, simple, economical, user-friendly and in an industrially viable manner.
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Page/Page column 9
(2011/07/09)
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- NOVEL INTERMEDIATES FOR SYNTHESIS OF CEPHALOSPORINS AND PROCESS FOR PREPARATION OF SUCH INTERMEDIATES
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A novel 4-halo-2-oxyimino-3-oxo butyric acid-N, N-dimethyl formiminium chloride chlorosulfate of formula (I) useful in the preparation of cephalosporin antibiotics, wherein X is chlorine or bromine; R is hydrogen, C1-4 alkyl group, an easily removable hydroxyl protective group, -CH2COOR5, or -C(CH3)2COOR5, wherein R5 is hydrogen or an easily hydrolysable ester group. The compound of formula (I) is prepared by reacting 4-halo-2-oxyimino-3-oxobutyric acid of formula (IV1), wherein X, R and R5 are as defined above, with N, N-dimethylformiminium chloride chlorosulphate of formula (VII), in an organic solvent at a temperature ranging from -30 °C to -15 °C. The cephalosporins that may be prepared from the intermediate include cefdinir, cefditoren pivoxil, cefepime, cefetamet pivoxil, cefixime, cefmenoxime, cefodizime, cefoselis, cefotaxime, cefpirome, cefpodoxime proxetil, cefquinome, ceftazidime, cefteram pivoxil, ceftiofur, ceftizoxime, ceftriaxone and cefuzonam.
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- Method for producing cephalosporins
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A method for producing cephalosporins 7-substituted with an amino-thiazolylacetic group by reacting 7-ACA or its derivatives having the amino group and the carboxyl protected with reactive derivatives of amino-thiazolylacetic acid.
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