28002-18-8

Usage

Originator

Lillacillin,Takeda,Japan,1973

Manufacturing Process

To a suspension of 1.08 parts by weight of 6-aminopenicillanic acid in 8 parts by volume of water is added 1.48 parts by weight of sodium bicarbonate. After the mixture is dissolved, a solution of 1.18 parts by weight of α-sulfophenylacetyl chloride in 10 parts by volume of diethylether is gradually added thereto. The mixture is stirred at a temperature in the neighborhood of 0°C for 1 hour. The aqueous layer is washed twice with 10 parts by volume of portions of ether and adjusted to pH 1.2 with cation exchange resin of polystyrene sulfonic acid type under constant cooling. Then the solution is washed twice with 15 parts by volume of portions of ethyl acetate, followed by extraction twice with 15 parts by volume of portions of n-butanol. The extracts are combined and washed twice with 15 parts by volume of portions of water and, then, extracted with an aqueous solution of sodium bicarbonate. The extract is adjusted to pH 6.5, washed with ether and lyophilized to give the sodium salt of α-sulfobenzylpenicillin. Yield is 1.2 parts by weight.

Therapeutic Function

Antibacterial

InChI:InChI=1/C16H18N2O7S2.2Na/c1-16(2)11(15(21)22)18-13(20)9(14(18)26-16)17-12(19)10(27(23,24)25)8-6-4-3-5-7-8;;/h3-7,9-11,14H,1-2H3,(H,17,19)(H,21,22)(H,23,24,25);;/q;2*+1/p-2/t9-,10?,11+,14-;;/m1../s1

Upstream product

• 551-16-6 6-Aminopenicillanic Acid 
• 40125-73-3 2-sulpho-2-phenylacetyl chloride 
• 103-82-2 phenylacetic acid 
• 41360-32-1 racemic α-sulfophenylacetic acid 
• 58569-36-1 Sulbenicillin 
• 39925-35-4 2-sulfo-2-phenylacetyl chloride 
• 19460-36-7 triethylammonium 6β-penicillanate 
• 39925-38-7 2-phenyl-2-sulfoacetic acid 

Relevant academic research and scientific papers

Sulbenicillin sodium intermediate and method for preparing sulbenicillin sodium therefrom

The invention belongs to the field of drug synthesis and in particular relates to a sulbenicillin sodium intermediate and a method for preparing sulbenicillin sodium thereform. The method specificallycomprises the following steps: reacting phenyl-2-sulfoacetic acid and isopropenyl acetate to produce an intermediate Z1; reacting the intermediate Z1 and a solution 6-APA, and further crystallizing out sulbenicillin sodium with sodium iso-octoate. Compared with the traditional acyl chloride method for preparing the intermediate, the method for producing the intermediate Z1 in the invention has the advantages that the problem that the raw materials and intermediate are damaged due to moisture absorption is solved, emission of acid gases such as sulfur dioxide and hydrogen chloride produced during acyl chloride preparation is reduced, the process is simple and easy to operate, and the solvent is convenient to recycle. The method for preparing sulbenicillin sodium from the intermediate Z1 inthe invention has the advantages of being low in cost, high in yield and excellent in quality, the prepared sulbenicillin sodium has the purity of 99%, and the method is mild in reaction condition, easy to operate and suitable for industrial production.

Preparation method of sulbenicillin sodium

The invention discloses a preparation method of sulbenicillin sodium. According to the invention, L-amino acid is firstly adopted to perform splitting on D, L-sulfonylphenylacetic acid to obtain D(-)-sulfonylphenylacetic acid, then D(-)-sulfonylphenylacetic acid is compounded with D, L-sulfonylphenylacetic acid to prepare a sulfonylphenylacetic acid mixture with D(-)-sulfonylphenylacetic acid to L(+)-sulfonylphenylacetic acid ratio being about 78%:22%, the sulfonylphenylacetic acid mixture is chlorinated and then reacts with 6-APA, and then reacts with sodium iso-octoate, to directly obtain asulbenicillin sodium mixture with the ratio of D(-)-sulbenicillin sodium to L(+)-sulbenicillin sodium being about 78%:22%. According to the invention, post-treatment process is simplified, no water isused in the step of producing sulbenicillin sodium, hydrolysis impurity level is reduced, product purity is more than 99.0%, and product mole rate is more than 90%.

Method for preparing D-sulbenicillin sodium

The invention discloses a method for preparing D-sulbenicillin sodium. The method includes steps of removing L-amino acid from L-amino acid salt of D-sulfophenylacetic acid in solvents and carrying out salt forming to obtain D-sulfophenylacetic acid salt; carrying out reaction on the D-sulfophenylacetic acid salt and acylating agents to obtain mixed acid anhydride; dissolving 6-APA in organic solvents under the effect of organic alkali; dropwise adding mixed acid anhydride solution into 6-APA solution, and carrying out sufficient reaction and after-treatment to obtain the D-sulbenicillin sodium. The D-sulfophenylacetic acid is an intermediate. The 6-APA is a matrix. The method has the advantages that the D-sulbenicillin sodium is prepared by the aid of novel synthetic routes, conditions are mild, the method includes stable process and is easy to implement, and the problems of instable processes of existing methods or insufficient optical purity of products and the like can be solved bythe aid of the method.

Preparation method of D-(-)-alpha-sulbenicillin sodium

The invention provides a preparation method of D-(-)-alpha-sulbenicillin sodium. The method comprises the following steps: taking alpha-sulfonylphenylacetic acid as an initial raw material, performinga reaction with carbonyl diimidazole to generate an acyl imidazoles acylating agent, and performing condensation with 6-APA to obtain a diastereomer of sulbenicillin; separating D-(-)-alpha-sulbenicillin by a recrystallization method, and forming salt with sodium hydroxide to obtain the D-(-)-alpha-sulbenicillin sodium. During a acid anhydrides preparation process, usage of a severe-toxicity substance is avoided, during a preparation process, recrystallization is used, and the optically pure D-(-)-alpha-sulbenicillin is prepared, cost is saved, operation is simplified, yield is increased, andthe method is in favor of industrial production and environment protection.

To facilitate the industrial production of synthesis method of sulbenicillin sodium (by machine translation)

The invention discloses a method of easy industrial production sulbenicillin sodium synthetic method, comprises the following steps: (1) sulfonation reaction; (2) alkalization reaction; (3) ion exchange; (4) chloro acylation reaction; (5) extracting sulphur benzene acetyl chloride; (6) preparation of (-) - α - D - sulbenicillin; (7) the preparation of (-) - α - D - sulbenicillin sodium. The invention relates to a convenient industrial production of synthetic method of sulbenicillin sodium, through reasonable synthetic route design, simplifies the sulphur benzene acetic acid disodium salt of the tedious operation, improves the yield; direct the synthetic process for preparing optically pure (-) - α - D - of sulbenicillin, saves the cost, more favorable to the industrialized production, market prospect. (by machine translation)

Preparing method for D(-)-sulbenicillin disodium

The invention provides a preparing method for D(-)-sulbenicillin disodium. The preparing method includes the concrete operation steps that D(-)-sulfophenylacetic acid, dichloroethane and a catalyst dimethylformamide are added into a reaction container, a BTC/C2H4Cl2 solution serves as an acylating chlorination agent, and a dichloroethane solution of D(-)-sulfophenylacetyl chloride is obtained through preparation; D(-)-sulfophenylacetyl chloride and 6-aminopenicillanic acid are prepared into D(-)-sulbenicillin disodium through condensation and refining. The BTC/C2H4Cl2 solution is adopted as the acylating chlorination agent, reaction efficiency is high, the number of side reactions is small, sulfur dioxide pollution is avoided, and the preparing method is of significance in environment-friendly production; acetone and 75% ethyl alcohol are adopted as solvent in the condensation reaction, the pH value is controlled to be seven through trimethylamine, the condensation reaction is carried out at about 10 DEG C, reaction conditions are moderate, the process is simple and easy to operate, the purity and the yield of the obtained D(-)-sulbenicillin disodium are high, and the preparing method is suitable for industrial production.