CN101974017A - Method for preparing penicillin-G-1-(S)-oxide - Google Patents
Method for preparing penicillin-G-1-(S)-oxide Download PDFInfo
- Publication number
- CN101974017A CN101974017A CN 201010502975 CN201010502975A CN101974017A CN 101974017 A CN101974017 A CN 101974017A CN 201010502975 CN201010502975 CN 201010502975 CN 201010502975 A CN201010502975 A CN 201010502975A CN 101974017 A CN101974017 A CN 101974017A
- Authority
- CN
- China
- Prior art keywords
- penicillin
- solution
- acid
- sulfoxide
- organic phase
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Cephalosporin Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for preparing penicillin-G-1-(S)-oxide. In the method, penicillin G is used as a raw material, and the oxidization of the penicillin G and the crystallization of penicillin-G-1-(S)-oxide which is the oxidization product of the penicillin G are performed at the same time. A penicillin-G-1-(S)-oxide crystal product is obtained by directly adding an oxidant into penicillin G organic phase solution, reacting and crystallizing, the oxidization reaction and the crystallization are performed at the same time, and the crystal product directly precipitates in organic solution. Compared with the conventional direct oxidization process, the method has the advantages that: the operation flow is simplified considerably; the operation is simple and convenient; the labor intensity is lowered; and the production period is shortened obviously. The process of extracting the penicillin G from the organic phase back to a water phase and the process of regulating pH value with diluted acid and crystallizing are saved, so the consumption of waster resources is reduced greatly, the discharge of waste acid liquor is reduced, and the problem of environmental pollution is alleviated obviously. The high-performance liquid chromatography (HPLC) content of the product reaches over 99.0 percent, and the weight yield of products with a main particle size over 30 mu m is over 90 percent.
Description
Technical field
The invention belongs to chemical engineering crystallization technique field, particularly a kind of is the method that raw material oxidation reactive crystallization prepares penicillin sulfoxide with penicillin.
Background technology
The chemistry of penicillin sulfoxide (Penicillin Sulfoxide) is called 4-Thia-1-azabicyclo[3.2.0] heptane-2-carboxylic acid, 3,3-dimethyl-7-oxo-6-[(phenylacetyl) amino]-(2S, 5R, 6R)-, 4-oxide, molecular formula is C
16H
18O
5N
2S, molecular weight are 350.2, and its chemical structural formula is as follows.
Penicillin sulfoxide is preparation 7-aminodesacetoxycephalosporanic acid (7-amino-3-desacetoxycephalosporanicacid, abbreviation 7-ADCA) important intermediate, and 7-ADCA is one of two big parent nucleus of cephalosporin analog antibiotic, is the important as precursors of producing cynnematins such as Cephalexin Monohydrate Micro/Compacted, S 578, Cephradine.So the quality of production quality of penicillin sulfoxide, yield height etc. directly has influence on the cephalosporin analog antibiotic medicine production.
At present, the preparation technology of penicillin sulfoxide mainly contains two kinds of methods:
One class is first esterification rear oxidation: the reaction of the carboxyl esterification on 3 in the penicillin is generated carboxylicesters, make penicillin sulfoxide through oxidizing reaction then, mention among the Japanese Patent JP 81142285: utilize benzyl halogen with penicillin salt reaction preparation in 6-8 hour penicillin carboxylicesters, oxidation prepares penicillin sulfoxide then, and yield is 90%.Another kind of method is directly the penicillin oxidation to be generated penicillin sulfoxide.This wherein has several method again: mention in the German Patent 2302745, with penicillin N-ethyl piperidine salt under-15 ℃ in methylene dichloride, oxidation makes penicillin sulfoxide in acetate-peracetic acid soln of 40%, yield is 89.1%.Mention in the United States Patent (USP) 4230620, potassium salt of penicillin is water-soluble, use the persulfuric acid oxidation after dilute hydrochloric acid is regulated pH value syncillin sulfoxide, HPLC purity 97.1%.Mention among the patent ES509855, potassium salt of penicillin is under assorted polycyclic acid and salt catalysis thereof, with H
2O
2Be oxidant reaction, rare acid for adjusting pH value makes penicillin sulfoxide, yield 91.8%.
Industrial main employing is at present carried out the method for penicillin oxidation and is produced in the aqueous solution: be raw material with the penicillin fermentation liquid, behind the organic extractant phase purifying, back extraction is to aqueous phase, crystallization obtains the penicillin crystal product, then the penicillin crystal product is dissolved in the aqueous solution, then carry out oxidizing reaction as oxygenant, regulate the pH value with aqueous sulfuric acid at last, prepare the penicillin sulfoxide crystal product with Peracetic Acid.This method is divided into: penicillin crystallization, penicillin oxidation, three parts of penicillin sulfoxide crystallization.The shortcoming of this method is: three processes are independently of one another, separately carry out, and flow process is complicated, and the production cycle is long, and quality product is relatively poor.Zhi Bei penicillin sulfoxide crystal product particle is tiny, coalescent in a large number in this way, filtration difficulty, and product colour is dark, and foreign matter content surpasses 30%.And in the crystallisation process of rare acid for adjusting pH value, consume great amount of water resources, and produce a large amount of waste acid liquors, both reduced production efficiency and output, also caused a large amount of wastes and pollution.
Summary of the invention
At the existing methods deficiency, the invention discloses a kind of method for preparing penicillin sulfoxide.Be a kind of be raw material with penicillin, a kind of method that the crystallization of the oxidation of penicillin and oxygenated products penicillin sulfoxide thereof is carried out simultaneously.
A kind of method for preparing penicillin sulfoxide, step is as follows:
(1) get the penicillin fermentation liquid or the preparation penicillin salt aqueous solution, penicillin concn is 6-70g/L in the solution, adds to stir decolouring 10-30 minute under the powdered active carbon room temperature in solution, and activated carbon dosage is the 2%-20% of penicillin quality in the solution; Filter, add isopyknic esters solvent in filtrate, regulate the pH value to 1.5-2.5 with dilute sulphuric acid, penicillin salt is converted into penicillinic acid, continuously stirring makes penicillinic acid be dissolved in ester class organic phase fully, obtains the ester class solution of penicillinic acid;
(2) under the room temperature, ester class solution left standstill layering with the penicillinic acid of step (1), separate ester class organic phase and water, after separating fully, ester class organic phase is added crystallizer, under-5 ℃-25 ℃, in the penicillinic acid organic phase, add oxygenant and carry out the oxidizing reaction crystallization, separate out crystal, the mass ratio of oxygenant and penicillin is 0.2: 1-0.4: 1;
(3) filter magma, deionized water wash, drying obtains the penicillin sulfoxide crystal product.
Described esters solvent is selected from one or two or more mixed solvents of butylacetate, ethyl acetate or methyl acetate.
Described oxygenant is the acetic acid solution or the aqueous hydrogen peroxide solution of Peracetic Acid, and its mass concentration is 8%-30%.
Described oxygenant rate of addition is the 1.5%-20% that per minute adds the oxygenant volume.
Temperature is 0 ℃-25 ℃ a pure water washing magma; Drying conditions is under 15-40 ℃, under the normal pressure dry 6-12 hour.
The penicillin sulfoxide crystal of the inventive method preparation, color is pure white, even particle size distribution, no agglomeration phenomena, product HPLC content reaches more than 99.0%, and main granularity is more than 30 μ m, and as shown in Figure 1, the product weight yield is more than 90%.Magma filters easily, washs, and product is easily dry, convenient solvent reclaiming.Novel process of the present invention, the oxidation and the crystallization of oxygenated products penicillin sulfoxide thereof of penicillin are integrated among a process, directly in the penicillin organic phase solution, add the oxidant reaction crystallization and obtain the penicillin sulfoxide crystal product, the oxidizing reaction crystallization is carried out simultaneously, and crystal product is directly separated out from organic solution.Traditional relatively direct oxidation method technology, this inventive method operating process is simplified greatly, and is easy and simple to handle, reduced labour intensity, and the production cycle obviously reduces.Save penicillin and stripped to water process and rare acid for adjusting pH value crystallisation process, greatly reduced the consumption of water resources, reduced the discharging of spent acid solution, obviously alleviated problem of environmental pollution from organic phase.
Description of drawings
Fig. 1: the penicillin sulfoxide product stereoscan photograph of the inventive method preparation;
The penicillin sulfoxide microphotograph of Fig. 2: embodiment 1;
The penicillin sulfoxide microphotograph of Fig. 3: embodiment 2;
The penicillin sulfoxide microphotograph of Fig. 4: embodiment 3;
The penicillin sulfoxide microphotograph of Fig. 5: embodiment 4;
The penicillin sulfoxide microphotograph of Fig. 6: embodiment 5;
The penicillin sulfoxide microphotograph of Fig. 7: embodiment 6.
Embodiment
Embodiment 1
Get the 500mL penicillin fermentation liquid, penicillin concn 6g/L in the fermented liquid.Take by weighing the 0.5g gac and add penicillin fermentation liquid, stir decolouring 10 minutes, after decolouring is finished, measure 500mL butylacetate adding fermented liquid and stir, regulate penicillin fermentation liquid pH value to 1.5 with the dilute sulfuric acid aqueous solution of 2mol/L and extract.Continue to stir after 30 minutes, solution is transferred in the separating funnel, butylacetate is separated with fermented liquid, obtain 6g/L penicillin butylacetate solution.It is added crystallizer, under-5 ℃ of constant temperature, stir.Measure concentration and be after 8% peracetic acid soln 7.5mL is cooled to-5 ℃, add crystallizer, carry out the oxidizing reaction crystallization with the speed of 0.12mL/min.After oxygenant drips and finishes, continue to stir 2 hours, reaction finishes to obtain white crystal, and vacuum filtration obtains white penicillin sulfoxide crystal.With twice of 0 ℃ of freezing deionized water wash magma.Under 15 ℃, normal pressure dry 12 hours, final crystal product content 99.34%, crystallisation process yield 94.5%.Products obtained therefrom is a rhabdolith, and main granularity is 63.66 μ m, and its (200 times) electromicroscopic photograph as shown in Figure 2.Adopt former technology, product particle is tiny, and filtration difficulty presents yellowly or light brown, and purity is less than 90%, and yield is less than 90%, needs recrystallization just can reach purity more than 99%.
Embodiment 2
Take by weighing the 35g penicillin salt, be dissolved in 500mL water, obtain the aqueous solution that penicillin salt concentration is 70g/L.Take by weighing the 1.5g gac and add the penicillin salt aqueous solution, stir decolouring 20 minutes, after decolouring is finished, measure the 500mL ethyl acetate adding penicillin salt aqueous solution and stir, regulate penicillin salt pH value of water solution to 2.0 with the dilute sulfuric acid aqueous solution of 1mol/L and extract.Continue to stir after 30 minutes, solution is transferred in the separating funnel, ethyl acetate is separated with the aqueous solution, obtain 70g/L penicillin ethyl acetate solution.It is added crystallizer, under 0 ℃ of constant temperature, stir.Measure concentration and be after 30% peracetic acid soln 46.7mL is cooled to 0 ℃, add crystallizer, carry out the oxidizing reaction crystallization with the speed of 2.33mL/min.After oxygenant drips and finishes, continue to stir 2.5 hours, reaction finishes to obtain white crystal, vacuum filtration.Obtain white penicillin sulfoxide crystal, use twice of 5 ℃ of freezing deionized water wash magma at last.At 20 ℃, normal pressure dry 8 hours down.Final crystal product content 99.38%, crystallisation process yield 90.1.%.Products obtained therefrom is a rhabdolith, and main granularity is 84.54 μ m, and its (200 times) electromicroscopic photograph as shown in Figure 3.
Embodiment 3
Get the 500mL penicillin fermentation liquid, penicillin concn 30g/L in the fermented liquid.Take by weighing the 2g gac and add penicillin fermentation liquid, stir decolouring 30 minutes, after decolouring is finished, measure 500mL methyl acetate adding fermented liquid and stir, regulate penicillin fermentation liquid pH value to 2.5 with the dilute sulfuric acid aqueous solution of 2mol/L and extract.Continue to stir after 30 minutes, solution is transferred in the separating funnel, methyl acetate is separated with fermented liquid, obtain 30g/L penicillin methyl acetate solution.It is added crystallizer, stir at 5 ℃ of following constant temperature.Measure concentration and be after 30% superoxol 12.5mL is cooled to 5 ℃, slowly add crystallizer, carry out the oxidizing reaction crystallization with the speed of 1.25mL/min.After oxygenant drips and finishes, continue to stir 3 hours, reaction finishes to obtain white crystal, vacuum filtration.Obtain white penicillin sulfoxide crystal, use twice of 10 ℃ of deionized water wash magma at last.At 30 ℃, normal pressure dry 6 hours down.Final crystal product content 99.01%, crystallisation process yield 91.3%.Products obtained therefrom is a rhabdolith, and main granularity is 57.92 μ m, and its (200 times) electromicroscopic photograph as shown in Figure 4.
Embodiment 4
Take by weighing the 13g penicillin salt, be dissolved in 500mL water and obtain the aqueous solution that penicillin salt concentration is 25g/L.Take by weighing the 1g gac and add the penicillin salt aqueous solution, stir decolouring 20 minutes, after decolouring is finished, measure 500mL ethyl acetate and butylacetate mixing solutions and add the stirring of the penicillin salt aqueous solution, regulate penicillin salt pH value of water solution to 2.0 with the dilute sulfuric acid aqueous solution of 1mol/L and extract.Continue to stir after 30 minutes, solution is transferred in the separating funnel, ethyl acetate is separated with the aqueous solution with the butylacetate mixing solutions, obtain 25g/L penicillin ethyl acetate and butylacetate mixing solutions.It is added crystallizer, under 15 ℃ of constant temperature, stir.Measure concentration and be 10% superoxol 37.5mL and maintain the temperature at 15 ℃, add crystallizer, carry out the oxidizing reaction crystallization with the speed of 7.5mL/min.After oxygenant drips and finishes, continue to stir 3 hours, reaction finishes to obtain white crystal, vacuum filtration.Obtain white penicillin sulfoxide crystal, use twice of 25 ℃ of deionized water wash at last.At 40 ℃, normal pressure dry 8 hours down.Final crystal product content 99.00%, crystallisation process yield 92.7%.Products obtained therefrom is a rhabdolith, and main granularity is 47.75 μ m, and its (200 times) electromicroscopic photograph as shown in Figure 5.
Embodiment 5
Get the 500mL penicillin fermentation liquid, fermented liquid concentration 15g/L.Take by weighing the 0.5g gac and add penicillin fermentation liquid, stir decolouring 10 minutes, after decolouring is finished, measure 500mL methyl acetate and butylacetate mixing solutions and add the fermented liquid stirring, regulate penicillin fermentation liquid pH value to 1.5 with the dilute sulfuric acid aqueous solution of 2mol/L and extract.Continue to stir after 30 minutes, solution is transferred in the separating funnel, methyl acetate is separated with fermented liquid with the butylacetate mixed phase, obtain 15g/L penicillin methyl acetate and butylacetate mixing solutions.It is added crystallizer, under 25 ℃ of constant temperature, stir.Measure concentration and be 20% peracetic acid soln 13.2mL and maintain the temperature at 25 ℃, add crystallizer, carry out the oxidizing reaction crystallization with the speed of 0.39mL/min.After oxygenant drips and finishes, continue to stir 2.5 hours, reaction finishes to obtain white crystal, vacuum filtration.Obtain white penicillin sulfoxide crystal, use twice of 5 ℃ of deionized water wash at last.At 25 ℃, normal pressure dry 8 hours down.Final crystal product content 99.45%, crystallisation process yield 90.5%.Products obtained therefrom is a rhabdolith, and main granularity is 35.44 μ m, and its (200 times) electromicroscopic photograph as shown in Figure 6.
Embodiment 6
Take by weighing the 25g penicillin salt, be dissolved in 500mL water and obtain the aqueous solution that penicillin salt concentration is 50g/L.Take by weighing the 1g gac and add the penicillin salt aqueous solution, stir decolouring 30 minutes, after decolouring is finished, measure 500mL ethyl acetate and methyl acetate mixing solutions and add the stirring of the penicillin salt aqueous solution, regulate penicillin salt pH value of water solution to 2.5 with the dilute sulfuric acid aqueous solution of 1mol/L and extract.Continue to stir after 30 minutes, solution is transferred in the separating funnel, ethyl acetate is separated with the aqueous solution with the methyl acetate mixed phase, obtain 50g/L penicillin ethyl acetate and methyl acetate mixing solutions.It is added crystallizer, under-5 ℃ of constant temperature, stir.Measure concentration and be after 20% superoxol 37.5mL is cooled to-5 ℃, add crystallizer, carry out oxidizing reaction with the speed of 1.89mL/min.After oxygenant drips and finishes, continue to stir 2 hours, reaction finishes to obtain white crystal, vacuum filtration.Obtain white penicillin sulfoxide crystal, use twice of 5 ℃ of deionized water wash at last.At 15 ℃, normal pressure dry 12 hours down.Final crystal product content 99.10%, crystallisation process yield 91.3%.Products obtained therefrom is a rhabdolith, and main granularity is 32.12 μ m, and its (200 times) electromicroscopic photograph as shown in Figure 7.
Open and the penicillin sulfoxide preparation method that proposes of the present invention, those skilled in the art can be by using for reference this paper content, and links such as appropriate change raw material, processing parameter realize.Method of the present invention and product are described by preferred embodiment, person skilled obviously can be in not breaking away from content of the present invention, spirit and scope to method as herein described with product is changed or suitably change and combination, realize the technology of the present invention.Special needs to be pointed out is, the replacement that all are similar and change apparent to those skilled in the artly, they are regarded as being included in spirit of the present invention, scope and the content.
Claims (5)
1. a method for preparing penicillin sulfoxide is characterized in that: be raw material with penicillin, the oxidation of penicillin and the crystallization of oxygenated products penicillin sulfoxide thereof are carried out simultaneously.
2. method for preparing penicillin sulfoxide is characterized in that step is as follows:
(1) get the penicillin fermentation liquid or the preparation penicillin salt aqueous solution, penicillin concn is 6-70g/L in the solution, adds to stir decolouring 10-30 minute under the powdered active carbon room temperature in solution, and activated carbon dosage is the 2%-20% of penicillin quality in the solution; Filter, add isopyknic esters solvent in filtrate, regulate the pH value to 1.5-2.5 with dilute sulphuric acid, penicillin salt is converted into penicillinic acid, continuously stirring makes penicillinic acid be dissolved in ester class organic phase fully, obtains the ester class solution of penicillinic acid;
(2) under the room temperature, ester class solution left standstill layering with the penicillinic acid of step (1), separate ester class organic phase and water, after separating fully, ester class organic phase is added crystallizer, under-5 ℃-25 ℃, in the penicillinic acid organic phase, add oxygenant and carry out the oxidizing reaction crystallization, separate out crystal, the mass ratio of oxygenant and penicillin is 0.2: 1-0.4: 1;
(3) filter magma, deionized water wash, drying obtains the penicillin sulfoxide crystal product.
3. method as claimed in claim 2 is characterized in that described esters solvent is selected from one or two or more mixed solvents of butylacetate, ethyl acetate or methyl acetate.
4. method as claimed in claim 2 is characterized in that described oxygenant is the acetic acid solution or the aqueous hydrogen peroxide solution of Peracetic Acid, and its mass concentration is 8%-30%.
5. method as claimed in claim 2 is characterized in that described oxygenant rate of addition is the 1.5%-20% that per minute adds the oxygenant volume.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010502975 CN101974017A (en) | 2010-10-11 | 2010-10-11 | Method for preparing penicillin-G-1-(S)-oxide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010502975 CN101974017A (en) | 2010-10-11 | 2010-10-11 | Method for preparing penicillin-G-1-(S)-oxide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101974017A true CN101974017A (en) | 2011-02-16 |
Family
ID=43573934
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010502975 Pending CN101974017A (en) | 2010-10-11 | 2010-10-11 | Method for preparing penicillin-G-1-(S)-oxide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101974017A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102757449A (en) * | 2012-06-29 | 2012-10-31 | 四川理工学院 | Preparation method of anhydrous penicillin sulfoxide |
| CN102964355A (en) * | 2012-12-17 | 2013-03-13 | 华北制药河北华民药业有限责任公司 | Preparation method of penicillin G sulfoxide |
| CN103467491A (en) * | 2013-09-29 | 2013-12-25 | 浙江昂利康制药有限公司 | Method for preparing cephalosporin midbody penicillin sulfoxide |
| CN113214292A (en) * | 2021-04-27 | 2021-08-06 | 华北制药股份有限公司 | Industrial production method for preparing penicillin sulfoxide by continuously oxidizing penicillin |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1201795A (en) * | 1998-05-22 | 1998-12-16 | 范伟光 | Preparation of 7-amino-deacetylated cefa-alkylation acid |
-
2010
- 2010-10-11 CN CN 201010502975 patent/CN101974017A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1201795A (en) * | 1998-05-22 | 1998-12-16 | 范伟光 | Preparation of 7-amino-deacetylated cefa-alkylation acid |
Non-Patent Citations (1)
| Title |
|---|
| 《江西化工》 20071231 栾伟丽等 "青霉素G亚砜对-硝基苄酯的合成工艺研究" 88-90 1-5 , 第3期 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102757449A (en) * | 2012-06-29 | 2012-10-31 | 四川理工学院 | Preparation method of anhydrous penicillin sulfoxide |
| CN102964355A (en) * | 2012-12-17 | 2013-03-13 | 华北制药河北华民药业有限责任公司 | Preparation method of penicillin G sulfoxide |
| CN102964355B (en) * | 2012-12-17 | 2015-07-01 | 华北制药河北华民药业有限责任公司 | Preparation method of penicillin G sulfoxide |
| CN103467491A (en) * | 2013-09-29 | 2013-12-25 | 浙江昂利康制药有限公司 | Method for preparing cephalosporin midbody penicillin sulfoxide |
| CN113214292A (en) * | 2021-04-27 | 2021-08-06 | 华北制药股份有限公司 | Industrial production method for preparing penicillin sulfoxide by continuously oxidizing penicillin |
| CN113214292B (en) * | 2021-04-27 | 2023-02-28 | 华北制药股份有限公司 | Industrial production method for preparing penicillin sulfoxide by continuously oxidizing penicillin |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP3854765B2 (en) | Method for purifying long-chain dicarboxylic acids | |
| CN101279997B (en) | Novel preparation of budesonide | |
| CN101974017A (en) | Method for preparing penicillin-G-1-(S)-oxide | |
| CN101570543B (en) | Preparation method of mezlocillin sodium solvent crystal | |
| CN101619069A (en) | Preparation method of cefotiam hexetil hydrochloride | |
| CN101475579B (en) | Stable cefuroxime sodium and preparation thereof | |
| CN103044239B (en) | Production method of sodium citrate | |
| CN107602651A (en) | A kind of preparation method of dehydroepiandros-sterone intermediate and dehydroepiandros-sterone | |
| CN113185485B (en) | Semi-synthesis method of dihydroquercetin | |
| CN106588681B (en) | A kind of method that L alanine is prepared using hydroxyproline waste water as raw material | |
| CN102351933A (en) | Method for preparing hydroxycobalamin salt | |
| CN103864802A (en) | Preparation method of high-purity asenapine maleate | |
| CN103882077A (en) | Normal temperature crystallization method of glucuronolactone | |
| CN102391288B (en) | Preparation methods of cefpirome intermediate and cefpirome | |
| CN102329268B (en) | Preparation method for 7-chlorine-5-oxo-2,3,4,5-tetrahydro-1H-1-benzoazepine | |
| CN101811979B (en) | Technology for producing injection-grade terramycin | |
| CN113336640B (en) | Method for reducing content of 1, 4-naphthalenedicarboxylic acid impurities | |
| CN104892370A (en) | Preparation method for reductive coenzyme Q10 | |
| CN100387586C (en) | Synthetic process of chiral 2-amido-1-(6-fluorine-3,4-dihydrobenzopyranyl) alCohol | |
| CN101768066B (en) | Preparation method and application of trichloroacetone with high purity | |
| CN113234080A (en) | Sitagliptin phosphate intermediate impurity and preparation method thereof | |
| CN112358489A (en) | Production method of industrial penicillin sulfoxide product | |
| CN101654457A (en) | Method for synthesizing mezlocillin sodium through solvent method | |
| CN112940062B (en) | Preparation method of 16-dehydroprogesterone | |
| CN114149447B (en) | Preparation method of 5-isosorbide mononitrate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20110216 |