- Synthetic method for ceftazidime side chain acid ethyl ester
-
The invention belongs to the technical field of medicine, and particularly relates to a synthetic method for ceftazidime side chain acid ethyl ester. The method comprises the following steps: adding sodium nitrite and ethyl acetoacetate into water, adding acetic acid for a reaction, performing extraction, and collecting the organic phase; performing distillation on the collected organic phase under normal and reduced pressure to obtain an oxime compound, performing dehydration treatment on the oxime compound, adding an alcohol, a catalyst and chlorine gas, and performing a chlorination reaction to obtain a chloride; performing a reaction on methanol, thiourea, a phase transfer catalyst, a buffer salt solution and the chloride to obtain an ethyl 2-(2-aminothiazole-4-yl)-2-hydroxyiminoacetate solution; and performing distillation on the ethyl 2-(2-aminothiazole-4-yl)-2-hydroxyiminoacetate solution under reduced pressure to obtain ethyl 2-(2-aminothiazole-4-yl)-2-hydroxyiminoacetate solution and a buffer salt, adding tert-butyl 2-bromoisobutyrate, a condensation catalyst and a solvent, and performing a reaction to obtain the ceftazidime side chain acid ethyl ester. The method is moreefficient, simpler, and more environmentally friendly and has higher quality and yield than a previous processes, and is suitable for large-scale industrial production.
- -
-
Paragraph 0047; 0049; 0050; 0052; 0054; 0055; 0057; 0059
(2020/03/06)
-
- An alternative procedure for preparation of cefdinir
-
Cefdinir, a broad spectrum third-generation cephalosporin for oral administration, was prepared by the following synthetic pathway: synthesis of diphenylmethyl 7β-amino-3-vinyl-3-cephem-4-carboxylate hydrochloride from 7-aminocephalosporanic acid (7-ACA), preparation of sodium 2-(2-tritylaminothiazol-4-yl)-(Z)-2-(tritylhydroxyimino) acetate from ethyl acetoacetate, coupling of both intermediaries to obtain diphenylmethyl 7β-[2-(2-tritylaminothiazol-4-yl)-(Z)-2-tritylhydroxyimino-3- vinyl-3-cephem-4-carboxylate and final cleavage of trityl and diphenylmethyl protective groups. This procedure allows to obtain better yields of cefdinir and to avoid the use of diketene during the synthesis of this antibiotic by the previously reported method.
- Gonzalez, Maritza,Rodriguez, Zalua,Tolon, Blanca,Rodriguez, Juan C.,Velez, Herman,Valdes, Barbara,Lopez, Miguel A.,Fini, Adamo
-
p. 409 - 418
(2007/10/03)
-
- (6R,7R)-7-[(Z)-2-(2-Aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido]-3-(1-pyridiniummethyl)-ceph-3-em-4-carboxylate and salts thereof
-
Cephalosporin antibiotics of the general formula STR1 (wherein Ra and Rb, which may be the same or different, each represent a C1-4 alkyl group or Ra and Rb together with the carbon atom to which they are attached form a C3-7 cycloalkylidene group; and R4 represents hydrogen or a 3- or 4-carbamoyl group) exhibit broad spectrum antibiotic activity, the activity being unusually high against gram-negative organisms such as strains of Pseudomonas organisms. A particular antibiotic compound of formula (I) possessing excellent antibacterial activity against strains of Pseudomonas organisms, as well as other valuable therapeutic properties, is (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimono) acetamido]-3-(1-pyridiniummethyl)-ceph-3-em-4 carboxylate. The invention also includes the non-toxic salts and non-toxic metabolically labile esters of compounds of formula (I). Also described are compositions containing the antibiotics of the invention and processes for the preparation of such antibiotics.
- -
-
-
- 7-[2-(2-Aminothiazol-4-yl)-2-(syn)-methoxyiminoacetamido] cephalosporins
-
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.
- -
-
-
- Cephalosporanic acid derivatives
-
Novel syn isomers of 7-amino-thiazolyl-acetamido-3-acetoxymethyl-cephalosporanic acid derivatives of the formula STR1 wherein R1 is selected from the group consisting of --CN, --CONH2 and --COOR1 ', R1 ' is selected from the group consisting of alkyl of 1 to 3 carbon atoms, hydrogen, alkali metal, alkaline earth metal, ammonium, magnesium and a non-toxic, pharmaceutically acceptable organic amine, A is selected from the group consisting of hydrogen, alkali metal, alkaline earth metal, ammonium, magnesium and a non-toxic, pharmaceutically acceptable organic amine, R' and R" are individually selected from the group consisting of hydrogen and alkyl of 1 to 3 carbon atoms with the STR2 group in the syn position with the proviso that when R1 is --COOR1 ' and R1 ' is hydrogen, A is hydrogen and when R1 is --COOR1 ' and R1 ' is an alkali metal, alkaline earth metal, magnesium, ammonium or an organic amine, A is an alkali metal, alkaline earth metal, magnesium ammonium or an organic amine having antibiotic properties and novel intermediates and processes.
- -
-
-
- 3-Acetoxymethyl-7-(iminoacetamido)-cephalosporanic acid derivatives
-
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.
- -
-
-
- 3-Acetoxymethyl-7-(iminoacetamido)-cephalosporanic acid derivatives
-
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.
- -
-
-
