Synthesis process of D-sulbenicillin sodium

A technology of sulbenicillin sodium and synthesis process, which is applied in the direction of organic chemistry, etc., can solve the problems of unstable reaction of intermediates, low product yield, long reaction time, etc., to achieve increased product yield, quicker reaction time, and improved yield. rate effect

Active Publication Date: 2022-01-28
HAINAN HAILING CHEMIPHARMA CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But in the existing process of preparing sulbenicillin sodium, it often occurs that its intermediate reaction is unstable and the reaction time is too long, thus affecting the final product yield is low, and problems such as insufficient purity, thus limiting D-sulbenicillin The industrialized production...

Method used

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  • Synthesis process of D-sulbenicillin sodium
  • Synthesis process of D-sulbenicillin sodium

Examples

Experimental program
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Embodiment 1

[0027] A kind of synthetic technique of D-sulfabenicillin sodium, comprises the following steps:

[0028] S1. Water, ethanol and 2-methyltetrahydrofuran were weighed and mixed according to a volume ratio of 4:4:1 to obtain a mixed solvent;

[0029] S2. Add 6-APA into the mixed solvent and mix, keep the constant temperature at 15°C, add NaOH solution dropwise to adjust the pH to 5.6, then raise the temperature to 23°C and perform ultrasonic dispersion treatment with a power of 150W for 8min, and keep the temperature at 23°C, and the pH is Under the condition of 5.6, the ethyl acetate solution of D-sulfophenylacetyl chloride is added dropwise, wherein, the mass concentration of D-sulfophenylacetyl chloride is 5%, and the mass ratio of 6-APA and D-sulfophenylacetyl chloride is 1: 1., the rate of addition is 1 / 45 of the total amount of the ethyl acetate solution of D-sulfophenylacetyl chloride added dropwise per minute to obtain the mixed initial liquid;

[0030] S3. Put the mixe...

Embodiment 2

[0035] A kind of synthetic technique of D-sulfabenicillin sodium, comprises the following steps:

[0036] S1. Water, ethanol and 2-methyltetrahydrofuran were weighed and mixed in a volume ratio of 4:8:2.5 to obtain a mixed solvent;

[0037] S2. Add 6-APA into the mixed solvent and mix, keep the constant temperature at 20°C, add dropwise NaOH solution to adjust the pH to 5.8, then raise the temperature to 25°C and perform ultrasonic dispersion treatment with a power of 200W for 10min, and keep the temperature at 25°C, and the pH is Under the condition of 5.8, the ethyl acetate solution of D-sulfophenylacetyl chloride is added dropwise, wherein, the mass concentration of D-sulfophenylacetyl chloride is 15%, and the mass ratio of 6-APA and D-sulfophenylacetyl chloride is 1: 1.3, the rate of addition is 1 / 50 of the total amount of the ethyl acetate solution of D-sulfophenylacetyl chloride added dropwise per minute to obtain the mixed initial solution;

[0038] S3. Put the mixed i...

Embodiment 3

[0042] A kind of synthetic technique of D-sulfabenicillin sodium, comprises the following steps:

[0043] S1. Water, ethanol and 2-methyltetrahydrofuran were weighed and mixed according to a volume ratio of 4:6:2.0 to obtain a mixed solvent;

[0044] S2. Add 6-APA to the mixed solvent and mix, keep the constant temperature at 18°C, add NaOH solution dropwise to adjust the pH to 5.7, then raise the temperature to 24°C and perform ultrasonic dispersion treatment with a power of 180W for 9 minutes, and keep the temperature at 24°C, and the pH is Under the condition of 5.7, the ethyl acetate solution of D-sulfophenylacetyl chloride is added dropwise, wherein, the mass concentration of D-sulfophenylacetyl chloride is 10%, and the mass ratio of 6-APA and D-sulfophenylacetyl chloride is 1: 1.15, the rate of addition is 1 / 50 of the total amount of the ethyl acetate solution of D-sulfophenylacetyl chloride added dropwise per minute, to obtain the mixed initial solution;

[0045] S3. Put...

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Abstract

The invention relates to a D-sulbenicillin sodium synthesis process, which comprises: S1, weighing water, ethanol and 2-methyltetrahydrofuran, and mixing to obtain a mixed solvent; S2, adding 6-APA into a mixed solvent, keeping the temperature at 15-20 DEG C, adjusting the pH value, increasing the temperature to 23-25 DEG C, carrying out ultrasonic dispersion treatment, and adding an ethyl acetate solution of D-sulfophenylacetyl chloride in a dropwise manner; S3, putting into a pressurized reaction kettle, filling with inert gas, keeping the pressurized pressure at 1.5-2.5 MPa, controlling the temperature at 40-60 DEG C, and reacting for 50-80 minutes; S4, adjusting the pH value, adding n-butyl alcohol, and uniformly mixing; and S5, cooling, dropwise adding a sodium bicarbonate solution, stirring at a constant temperature, collecting a water-phase extracting solution, adding absolute ethyl alcohol and acetone, and carrying out a reaction to obtain a D-sulbenicillin sodium finished product. According to the synthesis process of the D-sulbenicillin sodium, the reaction is milder, the yield of the final product is obviously improved, the purity of the D-sulbenicillin sodium can be 96% or above, and the synthesis process is more suitable for industrial production.

Description

technical field [0001] The invention relates to the technical field of D-sulfbenicillin sodium, in particular to a synthesis process of D-sulfbenicillin sodium. Background technique [0002] Sulbenicillin sodium is a broad-spectrum semi-synthetic penicillin antibiotic, which has antibacterial effects on various Gram-negative bacteria such as Enterobacteriaceae bacteria, Pseudomonas aeruginosa, Haemophilus influenzae, and Neisseria spp. In the treatment of pneumonia, urinary tract infection, complicated skin and soft tissue infection and sepsis caused by Pseudomonas aeruginosa, some Proteus and other Gram-negative bacteria. [0003] Sulbenicillin sodium is mainly composed of α-sulfophenylacetyl and 6-APA. At present, the common preparation method of sulfbenicillin sodium is mainly to prepare sulfophenylacetic acid into acid chloride and then condense with 6-APA, or prepare sulfophenylacetic acid triethylamine salt into mixed acid anhydride and then condense with 6-APA. synt...

Claims

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Application Information

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IPC IPC(8): C07D499/16C07D499/62C07D499/18C07D499/12
CPCC07D499/16C07D499/62C07D499/18C07D499/12
Inventor 陆一峰路国荣黄有兴
Owner HAINAN HAILING CHEMIPHARMA CORP
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