- A spore proper logical sequence of the ester preparation method
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The invention belongs to the technical field of medicines and particularly relates to a preparation method of cefditoren pivoxil. The preparation method particularly includes following steps: (1) carrying out a reaction between cefditoren mother nucleus 7ATCA and AE-activated ester with dichloromethane as a solvent under an alkaline condition at 0-5 DEG C; (2) performing extraction with pure water and adding a sodium iso-octoate/acetone solution to obtain cefditoren sodium; (3) carrying out a reaction between the cefditoren sodium and iodomethyl pivalate under the alkaline condition at -40 DEG C to obtain a cefditoren pivoxil solution; (4) adding pure water to separate out a crystal to obtain a crude product of the cefditoren pivoxil. The technical scheme also comprises steps of dissolving the crude product of the cefditoren pivoxil in a mixed solution including dichloromethane and anhydrous ethanol, washing the material solution with a 1% sodium bicarbonate solution and pure water, collecting an organic phase, and performing a pressure-reducing evaporate-drying process to obtain the cefditoren pivoxil being higher than 99% in purity and less in impurities. The preparation method is simple in operation, is easy to control, is high in yield, allows the raw material to be obtained easily and is suitable for industrialized large-scale production.
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Paragraph 0035; 0036; 0037; 0044; 0048; 0052; 0062
(2018/09/02)
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- A method for preparing spore proper logical sequenceester
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The invention belongs to the field of medicine synthesis, and particularly relates to a preparation method of cefditore. The method comprises the following steps that (1) under the photophobic condition, 7-ATCA and AE-active ester are added into methylene dichloride; catalysts are added; the temperature is lowered to 0 to 5 DEG C; triethylamine is added to obtain cefdiporen acid; a water solution of organic amine is added into organic solvents containing dissolved cefdiporen acid; crystal separation is carried out to obtain organic amine salts of the cefdiporen acid; (2) the organic amine salts of the cefdiporen acid take a reaction with iodomethyl pivalate under the existence of tetrabutylammonium bromide and sodium carbonate in N,N-dimethyl formamide to obtain the cefditore. The preparation method has the advantages that the organic amine salts of the cefdiporen acid are used; the defects of difficult storage and poor stability of the sodium salts of the cefdiporen acid are effectively avoided; E-shaped isomers are effectively removed; meanwhile, the esterification condition is optimized, so that the purity of final products is higher.
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Paragraph 0035; 0036
(2017/08/25)
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- Preparation method of cefditoren pivoxil
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The invention discloses a preparation method of an important antibiotic cefditoren pivoxil. The preparation method comprises that 7-ATCA as a raw material is bonded to an AE active ester under base catalysis so that cefditoren acid is obtained, the cefditoren acid and sodium bicarbonate undergo a reaction to produce a salt, and the salt and cefditoren pivoxil undergo a replacement reaction under alkaline conditions to produce 2, 2-dimethylpropionyloxy(6R, 7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-[(Z)-2-(4-methyl-1, 3-thiazolyl-5-yl)vinyl]-8-oxo-5-thia-1-azabicyalo[4. 2. 0]octyl-2-ene-2-formate. The preparation method has the advantages of low cost, simple operation, high purity, use of cheap and easily available raw materials, industrial production feasibility and small pollution.
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Paragraph 0007; 0010
(2017/02/24)
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- DEPLETION OF ISOMER IN CEPHALOSPORIN ANTIBIOTIC
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The present invention relates to the process for the depletion of E isomer of Cefditoren sodium of formula (I).
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Page/Page column 5
(2008/06/13)
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- PREPARATION OF INTERMEDIATE FOR 3-[2-(4-METHYLTHIAZOLE-5-YL)VINYL] CEPHALOSPORINS
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The present invention relates to the preparation of 4-methylthiazol-5-carboxaldehyde of Formula I, and use thereof as an intermediate in preparation of 3-[2-(4-methylthiazole-5-yl)vinyl] cephalosporins.
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Page/Page column 12
(2008/06/13)
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- DEPLETION OF E-ISOMERS IN PREPARATION OF Z-ENRICHED 3-(2-SUBSTITUTED VINYL) CEPHALOSPORINS
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The present invention relates to depleting E-isomers of 3-(2-substituted vinyl) cephalosporins from a Z/E mixture of the same by selective crystallization techniques. The present invention to Z-enriched compounds comprising less than 5 % E-isomer.
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Page/Page column 18-19
(2008/06/13)
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- PROCESS FOR SELECTIVE PREPARATION OF Z-ISOMER OF CEFDITOREN AND PHARMACEUTICALLY ACCEPTABLE SALTS AND ESTERS THEREOF
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The present invention relates to a selective process for preparation of Z-isomer of cefditoren of Formula I and pharmaceutically acceptable salts and esters thereof. cefditoren possesses a wide spectrum of antibacterial activity against Gram-positive and Gram-negative bacteria.
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Page/Page column 15-16
(2008/06/13)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF CEFDITOREN
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The present invention relates to an improved process for the preparation of Cefditoren of formula (I), the said process comprising the steps of: i) converting the compound of formula (II) to a compound of the formula (III) using TPP and sodium iodide in the presence of THF, water, and base; ii) reacting the compound of formula (III) with 4-methyl-5-formyl-thiazole to produce a compound of formula (IV); iii) deesterifying the compound of the formula (IV) to yield compound of formula (V); iv) converting the compound of formula (V) to compound of formula (VI) in the presence of a base and solvent; v) converting the compound of formula (VI) into compound of formula (VII) by enzymatic hydrolysis; and vi) reacting compound of formula (VII) with compound of formula (VIII) in the presence of solvent and base to produce compound of formula (I).
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- Synthesis and oral activity of pivaloyloxymethyl 7-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3(Z)-(4-methylt hiazol-5-yl)vinyl-3-cephem-4 carboxylate (ME1207) and its related compound
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7-[2-(2-Aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3(Z)-(4-methylth iazol-5-yl)vinyl-3-cephem-4-carboxylic acid (11, ME1206) and its 3-trans isomer (13) were prepared to test antibacterial activity. These compounds exhibited excellent antibacterial activity against both gram-positive and gram-negative bacteria, including β-lactamase producing strains. The pivaloyloxymethyl esters (12 and 14) of the compounds (11 and 13) were prepared by esterification with pivaloyloxymethyl iodide. Among them, pivaloyloxymethyl 7-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3(Z)-(4-methylt hiazol-5-yl)vinyl-3-cephem-4-carboxylate (12, ME1207) showed good urinary recovery after oral administration in mice.
- Sakagami,Atsumi,Yamamoto,Tamura,Yoshida,Nishihata,Fukatsu
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p. 2433 - 2436
(2007/10/02)
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