- A method for the preparation of cefixime
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The invention discloses a method for preparing cefixime. The method comprises the following steps: (A), adding quantitative 7-phenylacetamide-3-chloromethyl-3-cephem-4-p-methoxybenzyl carboxylate, magnesium powder and a solvent into a reaction container, and reacting at the temperature of 10-100 DEG C for 1-5 hours; (B), adding quantitative formaldehyde into the reaction system, and reacting at the temperature of 10-100 DEG C for 1-5 hours; (C) cooling to room temperature, dripping a proper amount of trifluoroacetic acid, stirring, performing after-treatment, thereby obtaining the mother nucleus of cefixime; (D) dissolving the obtained mother nucleus of cefixime in a proper amount of solvent, slowly adding quantitative cefixime side chain at the temperature of 10-30 DEG C, and reacting for 1-5 hours; and (E), performing after-treatment, thereby obtaining a cefixime trihydrate, wherein the solvents in the steps A and D refer to tetrahydrofuran, ethers with the carbon atom number of 1-10 and alkyl tetrahydrofuran with the carbon atom number of 1-10. The method disclosed by the invention is easy to operate, fewer in three wastes and convenient in aftertreatment and is an economical and practical technology.
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Paragraph 0034; 0036; 0037
(2017/04/07)
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- Method of synthesizing cefixime
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The invention discloses a method for synthesizing cefixime. The method comprises the following steps: (1) carrying out an amidation reaction between MICA ((Z)-2-(methoxycarbonylmethoxyimino)-2-(2-aminothiazol-4-yl)acetic acid) sulfur-phosphorous active ester and 7-AVCA to obtain cefixime methyl ester, wherein the structure of the MICA sulfur-phosphorous active ester is as shown in the formula (II); (2) hydrolyzing the cefixime methyl ester to obtain cefixime. According to the synthesizing method, a new MICA active ester, namely (z)-2-(2-amino-4-thiazolyl)-methoxycarbonyl methylene imino-acetic acid-diethyl phosphoryl active ester, is adopted, a byproduct diethyl phosphate has small toxicity; and the diethyl phosphate is liquid and can be easily removed, the method is simple in steps and is high in yield.
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- PROCESS FOR THE PREPARATION OF CEFIXIME
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The present invention provides an improved process for the preparation of Cefixime of formula (I), a cephalosporine antibiotic with an improved quality in regard to color and solubility.
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Page/Page column 9-10
(2008/06/13)
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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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- Thioester derivatives of thiazolyl acetic acid and their use in the preparation of cephalosporin compounds
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The present invention provides novel thioester derivatives of thiazolyl acetic acid of the general formula (I), wherein, R1represents H, trityl, CH3, or CRaRbCOOR3, in which Raand Rb, independently of one another, represents hydrogen or methyl and R3represents H or C1-C7alkyl; and R2represents C1-C4alkyl or phenyl. The invention also provides a method for preparation of the thioester derivatives and reaction of the thioester derivatives with cephem carboxylic acids to produce cephalosporin antibiotic compounds having general formula (II), wherein, R1represents H, trityl, CH3, or CRaRbCOOR3, in which Raand Rb, independently of one another, represents hydrogen or methyl and R3represents H or C1-C7alkyl; R4is CH3, —CH═CH2, CH2OCH3, CH2OCOCH3, and R5is H or a salt or a carboxylic protecting group, comprising, acylating a compound of formula (III), wherein, R4and R5are defined as above, and R6is H or trimethylsilyl; with a compound of formula (I).
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