![(6R,7R)-7-Amino-3-methoxymethyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (R)-1-(2,2-dimethyl-propionyloxy)-ethyl ester; hydrochloride](/Databaselist/images/loading.webp)
24701-69-7Relevant academic research and scientific papers
Preparation method of cefpodoxime acid
-
Paragraph 0028-0029, (2021/07/31)
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.
A PROCESS FOR ALKYLATING THE HYDROXYMETHYL GROUP AT POSITION -3 OF CEPHALOSPORINS
-
Page/Page column 14; 15, (2017/09/27)
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).
Preparation method of 7-amino-3-methoxymethyl-3-cephem-4-carboxylic acid
-
Paragraph 0025; 0026; 0027; 0028; 0029; 0030; 0031; 0032, (2017/08/28)
The invention discloses a preparation method of 7-amino-3-methoxymethyl-3-cephem-4-carboxylic acid, and relates to the technical field of preparation of pharmaceutical intermediates. The method includes the steps that under the protection of nitrogen, 7-aminocephalosporanic acid, a silane reagent and an imidazole catalyst are stirred for 0.5-2 h at 30-35 DEG C in a water-soluble organic solvent; then, the mixture is cooled to 0-5 DEG C, methanesulfonic acid, trimethyl borate and methyl alcohol are added, a methoxylation reaction is conducted with the temperature controlled to be 0-5 DEG C, and 7-amino-3-methoxymethyl-3-cephem-4-carboxylic acid is obtained, wherein the silane reagent is hexamethyldisilazane or trimethylchlorosilane or N,O-bis(trimethylsilyl)acetamide or dimethoxydimethylsilane. According to the method, the product purity is high, the impurity content is low, operation is easy and convenient, refining steps are simplified, production cost is reduced, and the method is suitable for industrial production.
Preparation method of cefpodoxime proxetil
-
Paragraph 0034; 0035; 0038; 0039, (2017/07/21)
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.
Synthesis method of cefpodoxime proxetil intermediate
-
Paragraph 0009, (2016/11/09)
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.
AN IMPROVED PROCESS FOR CEFPODOXIME ACID
-
Page/Page column 8, (2013/04/10)
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.
AN IMPROVED PROCESS FOR THE PREPARATION OF CEFPODOXIME ACID
-
Page/Page column 8, (2011/07/09)
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.
Synthesis of HR 916 K: An efficient route to the pure diastereomers of the 1-(pivaloyloxy)ethyl esters of cephalosporins
Defossa, Elisabeth,Fischer, Gerd,Gerlach, Uwe,Hoerlein, Rolf,Isert, Dieter,Krass, Norbert,Lattrell, Rudolf,Stache, Ulrich,Wollmann, Theo
, p. 1743 - 1749 (2007/10/03)
HR 916 K (5), the 1-(S)-(pivaloyloxy)ethyl prodrug ester of the cephalosporin cefdaloxime, exhibits a significantly higher oral bioavailability than the 1-(R) diastereomer HR 916 J. An efficient synthesis of HR 916 K was developed. The separation of the diastereomers was achieved by precipitation of the 1-(R)-hydrochloride 9 followed by crystallization of the 1-(S)-amine 10 (de > 96%). The 1-(R) diastereomer 9 was recycled by acidic saponification or enzymatic cleavage to AMCA (7). The amine 10 was acylated with mercaptobenzothiazole thioesters or mixed anhydrides, prepared from carboxylic acids 13 and 14, in almost quantitative yield. Deprotection of the oxime and formation of the tosylate proceeded in one step. Using thioester 18, we obtained HR 916 K (5) from AMCA (7) in 42% yield. VCH Verlagsgesellschaft mbH, 1996.
Synthesis of HR 916 B: The first technically feasible route to the 1-(pivaloyloxy)ethyl esters of cephalosporins
Fleischmann, Klaus,Adam, Friedhelm,Duerckheimer, Walter,Hertzsch, Winfried,Hoerlein, Rolf,Jendralla, Heiner,Lefebvre, Christian,Mackiewicz, Philippe,Roul, Jean-Michel,Wollmann, Theo
, p. 1735 - 1741 (2007/10/03)
An efficient synthesis of HR 916 B (4), the orally active 1-(RS)-(pivaloyloxy)ethyl prodrug ester of the cephalosporin cefdaloxime, was developed and applied on a multi-kg scale. AMCA (8) was prepared by exchange of the acetoxy group of fermentation product ACA (7) with the nucleophile methanol under acidic conditions. Its 7-amino group was acylated with mixed anhydride 14 to give 15. Carboxylic acid 15 was esterified with iodohydrin ester 27 or bromohydrin ester 30, respectively, to provide the acylal 16. Simultaneous removal of both the amino- and the oximo-protecting group furnished the prodrug HR 916 3, which was purified and stabilized by precipitation of its tosylate salt 4. The overall yield of 4 (ratio 5/6 = 0.65) was 39% relative to AMCA (8) (four steps), 15% relative to ACA (7) (five steps). VCH Verlagsgesellschaft mbH, 1996.
Process for the production of 7-ACA derivatives
-
, (2008/06/13)
The invention provides an improved process for the production of 7-amino-3-alkoxymethlycephem-4-carboxyl acid derivatives.
