- Antibiotic-improved cefmenoxime hydrochloride synthesis process
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The invention discloses an antibiotic-improved cefmenoxime hydrochloride synthesis process, which comprises the following steps: step 1, preparation of 1-methyl-5-sulfydryl-1H-tetrazole, step 2, preparation of 2-(2-amino-4-azolyl)-2(Z)-methoxyimino ethyl acetate; step 3, preparation of 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid; step 4, preparation of 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid-2-benzothiazole thioester; step 5, preparation of 7-amino-3-(1-methyl-1H-tetrazole-5-thiomethyl)cephalosporanic acid hydrochloride (7-ACA-MMT. HC1); and step 6, preparation of cefmenoxime hydrochloride; domestic raw materials are adopted, the raw materials are cheap and easy to obtain in the synthesis route, the synthesis cost is reduced, and synthesis is improved; the improved process has the advantages of low raw material cost, simplicity in operation and suitability for industrial production.
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Paragraph 0042-0044
(2021/02/06)
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- Clean preparation process of aminothiazoly loximic acid
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The invention discloses a clean preparation process of aminothiazoly loximic acid, and belongs to the technical field of organic synthesis. The method comprises the following steps: (1) dropwise adding sulfuric acid into ethyl acetoacetate and calcium nitrite for oximation, separating out a calcium sulfate solid, filtering and washing wet calcium sulfate powder to obtain calcium sulfate, adding sodium carbonate into a washing solution and filtrate, and dropwise adding dimethyl sulfate for methylation of oxime; (2) after completion of the cyclization reaction, carrying out phase splitting, dehydrating an organic phase, then carrying out halogenation, adding water for quenching, carrying out phase splitting, taking strongly acidic water as a water phase and a halide as an organic phase, dropwise adding the halide into thiourea, carrying out a cyclization reaction, adding trichloromethane after completion of the cyclization reaction, and carrying out phase splitting to remove the water phase so as to obtain an ethyl aminothiazoxylate trichloromethane solution; and (3) dropwise adding liquid caustic soda, hydrolyzing, carrying out phase splitting after the reaction is finished, removing the organic phase, decolorizing the water phase, and dropwise adding the quenched water phase until the aminothiazoly loximic acid is completely separated out. The method produces less three wastes, can realize resource recycling, and is high in product yield, simple to operate and easy to realize.
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Paragraph 0030-0032; 0034-0036; 0038-0040
(2021/04/17)
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- Method for continuously synthesizing ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate
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The invention discloses a method for continuously synthesizing ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate, and belongs to the field of cephalosporin medicine synthesis. According to the method, a continuous reaction device is utilized, 4-chloro-2-methoxyimino ethyl acetoacetate reaction liquid and a thiourea solution are added into a reactor according to a certain proportion, a certain temperature is kept, a soda ash solution is used for adjusting the pH value, the reaction liquid overflows to a cooler to be cooled, a product is obtained after filtering and washing, the liquid phasepurity is larger than 99.5%, and the yield is 85%-93%. The method has the advantages that the synthesis of ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate realizes continuous reaction, the variable control in the reaction process is more efficient and timely, the product quality stability is obviously improved, and meanwhile, as the continuous reaction is realized, the heat in the reaction process is effectively controlled, the energy can be effectively saved, the production cost is reduced, and the method is suitable for industrial large-scale production.
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Paragraph 0028
(2020/05/14)
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- Method for preparing ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate
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The invention relates to a method for preparing ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate. The ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate is prepared by sequentially performing oximation reaction of a raw material ethyl acetoacetate, methylation reaction, bromination reaction and cyclization reaction in the same reactor. According to the method for preparing the ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate, each reaction step can be continuously executed in the same reactor without extraction separation treatment, and moreover, only one solvent is used for the reactions, so that purification treatment of an intermediate product and a product is greatly simplified, influence of purification operation of extraction, solvent evaporation and the like on the stability and yield of the intermediate product and the yield of the product is reduced, the yield and quality of the product are remarkably improved, the production cost is reduced, and the method is applicable to industrial production.
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Paragraph 0014; 0016; 0020; 0026
(2017/08/29)
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- 7-[2-(2-Aminothiazol-4-yl)-2-(syn)-methoxyiminoacetamido] cephalosporins
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A 7-[2-(2-aminothiazol-4-yl)-2-(syn)-methoxyiminoacetamido] cephalosporin derivative of the formula; STR1 wherein R3 is hydrogen or a residue of a nucleophilic compound; R2 NH is an amino group which may optionally be protected, pharmaceutically acceptable salt or ester thereof, is found to have excellent anti-bacterial activity against a broad spectrum of bacteria inclusive of gram-negative bacteria such as Escherichia coli, Serratia marcescens, Proteus rettgeri, Enterobacter cloacae and Citrobacter freundii. Thus, this compound may be used for an antibacterial agent in therapeutical purposes.
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- 3-Acetoxymethyl-7-(iminoacetamido)-cephalosporanic acid derivatives
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Compounds of the formula STR1 wherein R is hydrogen, R' is selected from the group consisting of alkenyl and alkynyl of 2 to 4 carbon atoms, A is selected from the group consisting of hydrogen, alkali metal and equivalents of an alkaline earth metal or magnesium and an organic amine base and the OR' group is in the syn position having antibiotic activity and process for their preparation.
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- Alkyloximes of 7-amino-thiazolyl-acetamido-cephalosporanic acids
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Novel alkyloximes of 7-amino-thiazolyl-acetamidocephalosporanic acids of the formula STR1 wherein R is selected from the group consisting of alkyl of 1 to 5 carbon atoms, cycloalkyl of 3 to 5 carbon atoms and --CH2 --SR', R' is selected from the group consisting of acyl of an alkanoic acid of 2 to 4 carbon atoms, 1-methyl-tetrazolyl and 2-methyl-1,3,4-thiadiazolyl, R1 is selected from the group consisting of hydrogen and a group easily removeable by acid hydrolysis or hydrogenolysis, R2 is selected from the group consisting of alkyl of 1 to 4 carbon atoms and alkenyl and alkynyl of 2 to 4 carbon atoms, A is selected from the group consisting of hydrogen, an alkali metal cation, an equivalent of an alkaline earth metal or magnesium, an organic amine base cation and an ester group easily removeable by acid hydrolysis or hydrogenolysis with the proviso that when R1 is hydrogen, A is not an ester group easily removeable by hydrogenolysis or acid hydrolysis and the wavy line means that OR2 is in one or the other of the two possible syn or anti isomeric positions having a very good antibiotic activity and novel processes and intermediates for their preparation.
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- 3-Acetoxymethyl-7-(iminoacetamido)-cephalosporanic acid derivatives
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Compounds of the formula STR1 wherein R is selected from the group consisting of hydrogen and groups easily removable by acid hydrolysis or hydrogenolysis, R' is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms, alkenyl and alkynyl of 2 to 4 carbon atoms and groups easily removable by acid hydrolysis or hydrogenolysis, A is selected from the group consisting of hydrogen, alkali metal and equivalents of an alkaline earth metal or magnesium and an organic amine base with the proviso that when R' is a group easily removable by acid hydrolysis or hydrogenolysis, R is also and when R' is hydrogen, R also is hydrogen and the wavy line means the OR' group may be in either one of the two possible syn or anti positions having antibiotic activity and process for their preparation.
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