CN115057788A - Preparation method of pharmaceutical grade low-impurity salbutamol sulfate - Google Patents
Preparation method of pharmaceutical grade low-impurity salbutamol sulfate Download PDFInfo
- Publication number
- CN115057788A CN115057788A CN202210576141.2A CN202210576141A CN115057788A CN 115057788 A CN115057788 A CN 115057788A CN 202210576141 A CN202210576141 A CN 202210576141A CN 115057788 A CN115057788 A CN 115057788A
- Authority
- CN
- China
- Prior art keywords
- salbutamol sulfate
- solution
- pharmaceutical grade
- steps
- following
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/10—Separation; Purification; Stabilisation; Use of additives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pulmonology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the technical field of pharmaceutical chemical preparation, in particular to a preparation method of pharmaceutical grade salbutamol sulfate with low impurity. The method comprises the following specific steps: weighing benzyl alcohol, ethanol and palladium carbon, putting into a reaction kettle, introducing hydrogen, heating and keeping the pressure until the hydrogenation reaction is finished to obtain a solution A; filtering to obtain filtrate B; pouring the mixture into a reaction bottle for cooling, dropwise adding concentrated sulfuric acid, adjusting the pH value, separating out crystals, and centrifuging to obtain a yellowish salbutamol sulfate crude product; dissolving the crude product in purified water, adding active carbon for decolorization, and filtering to obtain salbutamol sulfate solution; pouring the solution into a reaction kettle, concentrating the volume of the solution under reduced pressure in a water bath environment, cooling, adding methanol, cooling, crystallizing, and centrifuging to obtain a salbutamol sulfate wet product; and (4) drying the wet product in a forced air drying oven to obtain a salbutamol sulfate refined product. The invention has simple process operation, low toxicity, high yield, high quality, little related substances, high product quality, low impurities and further reduced production cost.
Description
Technical Field
The invention relates to the technical field of pharmaceutical chemical preparation, and particularly relates to a preparation method of pharmaceutical grade low-impurity salbutamol sulfate.
Background
Salbutamol sulfate (Albuterol sulfate), also known as salbutamol sulfate, molecular weight: 33739, formula: (C) 13 H 21 NO 3 ) 2 ·H 2 SO 4 Melting point 180 ℃, water-soluble and ethanol-insoluble;
structural formula (xvi):
salbutamol sulphate is the first highly selective 2-receptor agonist with a bronchodilatory action of sufficient strength to be used clinically in the treatment of various types of tract obstruction. Such as bronchospasm of patients with bronchial asthma, Chronic Obstructive Pulmonary Disease (COPD), asthmatic tracheitis and emphysema, and has good therapeutic effect.
The preparation method commonly used for salbutamol sulfate in the prior art mainly comprises the following three methods: 1. starting from p-hydroxyacetophenone, brominating, hydrolyzing, aminating, hydrolyzing, neutralizing, catalytic hydrogenating, hydrogenolyzing and salifying for 8 steps to obtain salbutamol sulfate, wherein the total yield is 11-13%. The method has the disadvantages of harsh reaction conditions, serious three-waste pollution and high cost. 2. The preparation method comprises the steps of carrying out Friedel-Crafts acylation on salicylaldehyde and acyl chloride serving as raw materials to obtain 4-bromoacetyl salicylaldehyde and 4 chloroacetyl salicylaldehyde, carrying out condensation, hydrolysis and salt formation one-bath reaction to convert the salicylaldehyde and the 4 chloroacetyl salicylaldehyde into [ (5-11-dimethylethyl) amino ] acetyl-2 hydroxybenzaldehyde hydrochloride, carrying out synergistic reduction on potassium borohydride and zinc chloride at normal temperature, and carrying out salt formation with sulfuric acid to obtain salbutamol sulfate, wherein the total yield is 20-33%. The method has simple steps, but the obtained salbutamol sulfate has low yield and higher impurity content. 3. Salicylaldehyde and tert-butylamine are used as starting raw materials, 2-chloro 1{ [ (1, 1-dimethylethyl) iminomethyl-4 hydroxyphenyl } -ethyl ketone is prepared through three steps of one-pot reaction of condensation, esterification and Fries rearrangement, then the 2-chloro 1{ [ (1, 1-dimethylethyl) iminomethyl-4 hydroxyphenyl } -ethyl ketone is converted into 5- { [ (1, 1-dimethylethyl) aminoacetyl }2 antelope benzaldehyde hydrochloride through three steps of one-pot reaction of condensation, hydrolysis and salt formation, then sodium methoxide neutralization, catalytic transfer hydrogenation reduction and salt formation are carried out, and salbutamol sulfate is obtained, and the total yield is 40% -50%. The method has the advantages of complex steps, high cost and low yield, and is not suitable for large-scale production.
Disclosure of Invention
The present invention is designed to solve at least one of the technical problems of the prior art, and therefore, an aspect of the present invention is to provide a method for preparing pharmaceutical grade salbutamol sulfate with low impurity content.
The preparation method comprises the following specific steps:
s1, weighing benzyl alcohol, ethanol and palladium carbon, putting the benzyl alcohol, the ethanol and the palladium carbon into a reaction kettle I, introducing hydrogen into the reaction kettle I, heating to carry out hydrogenation reaction, and keeping the pressure until the hydrogenation reaction is finished to obtain a solution A;
s2, filtering the solution A obtained in the step S1 to obtain a filtrate B;
s3, pouring the filtrate B obtained in the step S2 into a reaction bottle for cooling, dropwise adding concentrated sulfuric acid, adjusting the pH value, separating out crystals, and centrifuging to obtain a yellowish salbutamol sulfate crude product;
s4, dissolving the yellowish salbutamol sulfate crude product obtained in the step S3 in purified water, adding activated carbon for decoloring, and filtering to obtain a salbutamol sulfate solution;
s5, pouring the salbutamol sulfate solution obtained in the step S4 into a reaction kettle II, concentrating the volume of the solution under reduced pressure in a water bath environment, cooling, adding methanol, cooling, crystallizing, and centrifuging to obtain a salbutamol sulfate wet product;
s6, the wet salbutamol sulfate product obtained in the step S5 is placed into a forced air drying oven to be dried, and a refined salbutamol sulfate product is obtained.
Preferably, the reaction kettle I in the S1 is vacuumized, then hydrogen is introduced, the introduction of hydrogen is stopped when the pressure is 3.0MPa, the reaction kettle is heated to 75-80 ℃ for hydrogenation reaction, the pressure is kept at 1.5-3.0MPa for 1 hours, and the pressure is kept at 1.5-3.0MPa when the pressure is less than 1.5 MPa.
Preferably, the mass ratio of the benzyl alcohol, the ethanol, the palladium carbon and the hydrogen in S1 is 0.5-1.5:4-8:0.01-0.03: 1-5.
Preferably, the filtering in S2 is to filter out palladium on carbon.
Preferably, the temperature in the S3 is reduced to 0-10 ℃; the concentration of the concentrated sulfuric acid in the S3 is 98%, and the pH value is adjusted to 6.
Preferably, the feeding mass ratio of the solution B to the concentrated sulfuric acid in the S3 is 0.5-1.5: 0.1-0.2.
Preferably, the feeding mass ratio of the salbutamol sulfate crude product, the purified water and the activated carbon in S4 is 0.5-1.5:1-3: 0.01-0.03; the filtration in S4 is to filter out activated carbon.
Preferably, the temperature of the water bath environment in the S5 is 45-50 ℃, the reaction kettle II is vacuumized, the volume of the solution is reduced to 1/2 of the original volume, the temperature is reduced to 30-40 ℃, methanol is added, and the temperature is reduced to 0-10 ℃ for crystallization for 1-2 hours; the effect of the addition of methanol is to dissolve impurities in the solution during crystallization, thereby reducing the impurity content of the salbutamol sulfate refined product.
Preferably, the feeding mass ratio of the salbutamol sulfate solution to the methanol in the S5 is 2-3: 0.5-1.5.
Preferably, the drying temperature of the forced air drying oven in the S6 is 75-80 ℃, and the drying time is 6 hours.
The invention has the following beneficial effects:
compared with the prior art, the method has the advantages of simple process operation, low toxicity, high yield, high quality, little related substances, high product quality, low impurity content and capability of further reducing the production cost. No catalyst is used, no high-temperature reaction is caused, the reaction condition is mild, the required equipment is simple, and the method is suitable for large-scale and industrial production. The required raw materials are cheap and easy to obtain, the operation is simple, and the three wastes are less, so that the method meets the requirement of environment-friendly production.
Additional aspects and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention.
Detailed Description
In order that the above objects, features and advantages of the present invention may be more clearly understood, the present invention will be described in further detail with reference to specific embodiments. It should be noted that the embodiments and features of the embodiments of the present application may be combined with each other without conflict.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, however, the present invention may be practiced otherwise than as specifically described and, therefore, the scope of the present invention is not limited by the specific embodiments disclosed below.
Example one
100g of benzyl alcohol, 600mL of ethanol and 2g of palladium carbon are weighed and placed into a 1000mL reaction kettle I, hydrogen is stopped to be introduced into the reaction kettle I when the pressure is 3.0MPa, the reaction kettle I is heated to 80 ℃ for hydrogenation reaction, the pressure is kept between 1.5 and 3.0MPa for 1 hour and is kept unchanged, when the pressure is lower than 1.5MPa, hydrogen (about 2.4kg) is introduced to keep the pressure between 1.5 and 3.0MPa all the time, and the palladium carbon is filtered out. And pouring the filtrate into a 1000ml reaction bottle, cooling to 0 ℃, dropwise adding 98% concentrated sulfuric acid (0.12kg), adjusting the pH value to 6, stopping dropwise adding, naturally separating out crystals, and centrifuging to obtain a salbutamol sulfate crude product.
And adding the salbutamol sulfate crude product into 1000ml of purified water for dissolving, adding 2g of active carbon for decoloring, and filtering the active carbon to obtain a salbutamol sulfate solution.
And pouring the salbutamol sulfate solution into a 1000ml reaction kettle II, concentrating the volume of the solution to 1/2 of the original volume under reduced pressure at the water bath temperature of 50 ℃, cooling to 30 ℃, adding 500g of methanol, cooling to 0 ℃, crystallizing for 2 hours, and centrifuging to obtain a wet salbutamol sulfate product.
And (3) putting the wet salbutamol sulfate product into a forced air drying oven for drying at the drying temperature of 80 ℃ for 6 hours to obtain 60g of a refined salbutamol sulfate product. The yield is as follows: 60 percent; the detected related substances have single impurity of 0.1 percent and total impurity of 0.3 percent.
Example two
100g of benzyl alcohol, 800mL of ethanol and 2g of palladium carbon are weighed and placed into a 1000mL reaction kettle I, hydrogen is stopped to be introduced into the reaction kettle I when the pressure is 3.0MPa, the reaction kettle I is heated to 80 ℃ for hydrogenation reaction, the pressure is kept between 1.5 and 3.0MPa for 1 hour and is kept unchanged, hydrogen (about 2kg) is introduced when the pressure is lower than 1.5MPa to keep the pressure between 1.5 and 3.0MPa all the time, and the palladium carbon is filtered out. And pouring the filtrate into a 1000ml reaction bottle, cooling to 0 ℃, dropwise adding 98% concentrated sulfuric acid (0.15kg), adjusting the pH value to 6, stopping dropwise adding, naturally separating out crystals, and centrifuging to obtain a salbutamol sulfate crude product.
And adding the salbutamol sulfate crude product into 1000ml of purified water for dissolving, adding 2g of active carbon for decoloring, and filtering the active carbon to obtain a salbutamol sulfate solution.
And pouring the salbutamol sulfate solution into a 1000ml reaction kettle II, concentrating the volume of the solution to 1/2 of the original volume under reduced pressure at the water bath temperature of 50 ℃, cooling to 30 ℃, adding 550g of methanol, cooling to 0 ℃, crystallizing for 2 hours, and centrifuging to obtain a wet salbutamol sulfate product.
And (3) putting the wet salbutamol sulfate product into a forced air drying oven for drying at 80 ℃ for 6 hours to obtain 59g of a refined salbutamol sulfate product. The yield is as follows: 59 percent of; the detected related substances have single impurity of 0.1 percent and total impurity of 0.3 percent.
EXAMPLE III
100g of benzyl alcohol, 700mL of ethanol and 2g of palladium carbon are weighed and placed into a 1000mL reaction kettle I, hydrogen is stopped to be introduced into the reaction kettle I when the pressure is 3.0MPa, the reaction kettle I is heated to 80 ℃ for hydrogenation reaction, the pressure is kept between 1.5 and 3.0MPa for 1 hour and is kept unchanged, hydrogen (about 2.6kg) is introduced when the pressure is lower than 1.5MPa, the pressure is kept between 1.5 and 3.0MPa all the time, and the palladium carbon is filtered out. And pouring the filtrate into a 1000ml reaction bottle, cooling to 0 ℃, dropwise adding 98% concentrated sulfuric acid (0.14kg), adjusting the pH value to 6, stopping dropwise adding, naturally separating out crystals, and centrifuging to obtain a salbutamol sulfate crude product.
And adding the salbutamol sulfate crude product into 1000ml of purified water for dissolving, adding 2g of active carbon for decoloring, and filtering the active carbon to obtain a salbutamol sulfate solution.
Pouring the salbutamol sulfate solution into a 1000ml reaction kettle II, concentrating the volume of the solution to 1/2 of the original volume under reduced pressure at the water bath temperature of 50 ℃, cooling to 30 ℃, adding 450g of methanol, cooling to 0 ℃, crystallizing for 2 hours, and centrifuging to obtain a salbutamol sulfate wet product.
And (3) putting the wet salbutamol sulfate product into a forced air drying oven for drying at the drying temperature of 80 ℃ for 6 hours to obtain 63g of a refined salbutamol sulfate product. The yield is as follows: 63%; the detected related substances have single impurity of 0.1 percent and total impurity of 0.3 percent.
The method for detecting the salbutamol sulfate impurity comprises the following steps:
taking a proper amount of the salbutamol sulfate refined product obtained in the embodiment of the invention, dissolving and diluting the salbutamol sulfate refined product with pure water to prepare a solution containing 2mg of the salbutamol sulfate refined product in 1ml of pure water as a test solution; precisely measuring 1ml of test solution, placing in a 100ml quantitative bottle, adding pure water to dilute to scale mark, and shaking to obtain control solution. According to the determination of high performance liquid chromatography (appendix V D), octadecylsilane chemically bonded silica is used as a filler, phosphate buffer solution and 0.08mol/L sodium dihydrogen phosphate solution (pH value is adjusted to 3.10+0.05 by phosphoric acid) -methanol (85: 15) are used as mobile phases, the detection wavelength is 276nm, and the separation degree of a salbutamol sulfate peak refined product and an adjacent impurity peak in the embodiment of the invention is in accordance with the requirement. Injecting 20 μ l of the control solution into a liquid chromatograph, and adjusting detection sensitivity to make the peak height of the main component chromatographic peak 20% of the full-scale range. And precisely measuring 20 mul of each of the test solution and the control solution, respectively injecting into a liquid chromatograph, and recording the chromatogram until the retention time of the main component peak is 12 times. And (3) displaying an impurity peak in a chromatogram of the test solution, comparing the peak area of a single impurity with the main peak area of the reference solution to obtain the single impurity amount, and comparing the sum of the peak areas of all impurities with the main peak area of the reference solution to obtain the total impurity amount.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and it is obvious to those skilled in the art that various modifications and variations can be made in the present invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A preparation method of pharmaceutical grade salbutamol sulfate with low impurity is characterized by comprising the following steps: the method comprises the following specific steps:
s1, weighing benzyl alcohol, ethanol and palladium-carbon, putting the benzyl alcohol, the ethanol and the palladium-carbon into a reaction kettle I, introducing hydrogen into the reaction kettle I, heating to carry out hydrogenation reaction, and keeping the pressure until the hydrogenation reaction is finished to obtain a solution A;
s2, filtering the solution A obtained in the step S1 to obtain a filtrate B;
s3, pouring the filtrate B obtained in the step S2 into a reaction bottle for cooling, dropwise adding concentrated sulfuric acid, adjusting the pH value, separating out crystals, and centrifuging to obtain a yellowish salbutamol sulfate crude product;
s4, dissolving the yellowish salbutamol sulfate crude product obtained in the step S3 in purified water, adding activated carbon for decoloring, and filtering to obtain a salbutamol sulfate solution;
s5, pouring the salbutamol sulfate solution obtained in the step S4 into a reaction kettle II, concentrating the volume of the solution under reduced pressure in a water bath environment, cooling, adding methanol, cooling, crystallizing, and centrifuging to obtain a salbutamol sulfate wet product;
s6, the wet salbutamol sulfate product obtained in the S5 is placed into a forced air drying oven to be dried, and a refined salbutamol sulfate product is obtained.
2. The method of claim 1, wherein the pharmaceutical grade salbutamol sulfate with low impurity content is prepared by the following steps: and (3) vacuumizing the reaction kettle I in the S1, introducing hydrogen, stopping introducing the hydrogen when the pressure is 3.0MPa, heating to 75-80 ℃ for hydrogenation reaction, keeping the pressure at 1.5-3.0MPa for 1 hours, and introducing the hydrogen when the pressure is less than 1.5MPa to keep the pressure at 1.5-3.0MPa all the time.
3. The method of claim 1, wherein the pharmaceutical grade salbutamol sulfate with low impurity content is prepared by the following steps: the mass ratio of the benzyl alcohol, the ethanol, the palladium carbon and the hydrogen in the S1 is 0.5-1.5:4-8:0.01-0.03: 1-5.
4. The method of claim 1, wherein the pharmaceutical grade salbutamol sulfate with low impurity content is prepared by the following steps: the filtration in S2 is to filter out palladium on carbon.
5. The method of claim 1, wherein the pharmaceutical grade salbutamol sulfate with low impurity content is prepared by the following steps: cooling to 0-10 ℃ in the S3; the concentration of the concentrated sulfuric acid in the S3 is 98%, and the pH value is adjusted to 6.
6. The method of claim 1, wherein the pharmaceutical grade salbutamol sulfate with low impurity content is prepared by the following steps: the feeding mass ratio of the solution B to the concentrated sulfuric acid in the S3 is 0.5-1.5: 0.1-0.2.
7. The method of claim 1, wherein the pharmaceutical grade salbutamol sulfate with low impurity content is prepared by the following steps: the mass ratio of the salbutamol sulfate crude product, the purified water and the activated carbon in S4 is 0.5-1.5:1-3: 0.01-0.03; the filtration in S4 is to filter out activated carbon.
8. The method of claim 1, wherein the pharmaceutical grade salbutamol sulfate with low impurity content is prepared by the following steps: and the temperature of the water bath environment in the S5 is 45-50 ℃, the reaction kettle II is vacuumized and then decompressed and concentrated to 1/2 of the original volume, the temperature is reduced to 30-40 ℃, methanol is added, and the temperature is reduced to 0-10 ℃ for crystallization for 1-2 hours.
9. The method for preparing salbutamol sulfate with low impurity in pharmaceutical grade according to claim 1, wherein the method comprises the following steps: the feeding mass ratio of the salbutamol sulfate solution to the methanol in the S5 is 2-3: 0.5-1.5.
10. The method of claim 1, wherein the pharmaceutical grade salbutamol sulfate with low impurity content is prepared by the following steps: and the drying temperature of the forced air drying oven in the S6 is 75-80 ℃, and the drying time is 6 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210576141.2A CN115057788A (en) | 2022-05-25 | 2022-05-25 | Preparation method of pharmaceutical grade low-impurity salbutamol sulfate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210576141.2A CN115057788A (en) | 2022-05-25 | 2022-05-25 | Preparation method of pharmaceutical grade low-impurity salbutamol sulfate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115057788A true CN115057788A (en) | 2022-09-16 |
Family
ID=83197689
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210576141.2A Pending CN115057788A (en) | 2022-05-25 | 2022-05-25 | Preparation method of pharmaceutical grade low-impurity salbutamol sulfate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115057788A (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1566076A (en) * | 2003-06-11 | 2005-01-19 | 新加坡纳米材料科技有限公司 | Synthetic method for superfine sulfuric acid and salbutamol |
| CN104356009A (en) * | 2014-10-22 | 2015-02-18 | 扬州市三药制药有限公司 | Production technology for synthetizing salbutamol sulphate |
| CN109761828A (en) * | 2019-02-26 | 2019-05-17 | 重庆康刻尔制药有限公司 | A kind of preparation method of salbutamol sulfate intermediate |
| CN110981740A (en) * | 2019-11-26 | 2020-04-10 | 安徽恒星制药有限公司 | Salbutamol sulfate impurity and preparation method thereof |
| CN113121369A (en) * | 2019-12-31 | 2021-07-16 | 天津药业研究院股份有限公司 | Preparation method of salbutamol sulfate |
| CN113801029A (en) * | 2020-06-16 | 2021-12-17 | 盈科瑞（天津）创新医药研究有限公司 | Preparation method of levalbuterol hydrochloride |
-
2022
- 2022-05-25 CN CN202210576141.2A patent/CN115057788A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1566076A (en) * | 2003-06-11 | 2005-01-19 | 新加坡纳米材料科技有限公司 | Synthetic method for superfine sulfuric acid and salbutamol |
| CN104356009A (en) * | 2014-10-22 | 2015-02-18 | 扬州市三药制药有限公司 | Production technology for synthetizing salbutamol sulphate |
| CN109761828A (en) * | 2019-02-26 | 2019-05-17 | 重庆康刻尔制药有限公司 | A kind of preparation method of salbutamol sulfate intermediate |
| CN110981740A (en) * | 2019-11-26 | 2020-04-10 | 安徽恒星制药有限公司 | Salbutamol sulfate impurity and preparation method thereof |
| CN113121369A (en) * | 2019-12-31 | 2021-07-16 | 天津药业研究院股份有限公司 | Preparation method of salbutamol sulfate |
| CN113801029A (en) * | 2020-06-16 | 2021-12-17 | 盈科瑞（天津）创新医药研究有限公司 | Preparation method of levalbuterol hydrochloride |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111646922B (en) | Synthetic method of 2- (4-bromo-2-cyano-6-fluorophenyl) acetic acid | |
| US20080051604A1 (en) | Process For Producing (Z)-1-Phenyl-1-Diethylaminocarbonyl-2-Aminomethylcyclopropane Hydrochloride | |
| CN110156670B (en) | Method for synthesizing a plurality of atorvastatin impurities at one time and application thereof | |
| CN112500291B (en) | Preparation and purification method of beta 2 receptor agonist intermediate | |
| CN115057788A (en) | Preparation method of pharmaceutical grade low-impurity salbutamol sulfate | |
| CN110002981B (en) | Method for preparing pseudo ionone | |
| CN114478290A (en) | Synthetic method of oseltamivir intermediate | |
| CN113603733A (en) | Preparation of glycolipid type ionic liquid and application of glycolipid type ionic liquid in glycolipid separation process | |
| CN112479938A (en) | Preparation method of N-cyclohexyl-2-aminoethanesulfonic acid | |
| CN105646617A (en) | Method for preparing tulathromycin | |
| CN112608242A (en) | Solvent-recycled meglumine production process | |
| CN111138354A (en) | Preparation method of isoniazid | |
| CN114262340B (en) | Preparation method of aminophenylboric acid | |
| CN112724181B (en) | Method for preparing Cangrelor intermediate adenosine-2-thioketone | |
| CN115677579B (en) | Preparation method of tetrahydropapaverine and intermediate thereof | |
| CN114249703B (en) | Preparation method of medical intermediate suitable for industrial amplification | |
| CN111087340B (en) | Preparation method of vilazodone intermediate | |
| CN112457206A (en) | Refining process of meglumine | |
| CN116514666A (en) | Preparation method of bromhexine hydrochloride | |
| CN117186000A (en) | Preparation method of quinoline compound | |
| CN115448847A (en) | Preparation method of salbutamol intermediate | |
| CN113943206A (en) | Preparation method of high-quality (R) -3-chloro-1, 2-propanediol | |
| CN117534644A (en) | Preparation method of alpinetin | |
| CN114671802A (en) | Preparation method of high-purity ebastine | |
| CN117534634A (en) | Preparation method of eperisone hydrochloride |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |