CN113880723A - Preparation method of betaine hydrochloride - Google Patents
Preparation method of betaine hydrochloride Download PDFInfo
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- CN113880723A CN113880723A CN202111348457.8A CN202111348457A CN113880723A CN 113880723 A CN113880723 A CN 113880723A CN 202111348457 A CN202111348457 A CN 202111348457A CN 113880723 A CN113880723 A CN 113880723A
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- betaine hydrochloride
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- betaine
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- 229960003403 betaine hydrochloride Drugs 0.000 title claims abstract description 28
- HOPSCVCBEOCPJZ-UHFFFAOYSA-N carboxymethyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC(O)=O HOPSCVCBEOCPJZ-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims abstract description 24
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000007864 aqueous solution Substances 0.000 claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims description 43
- 238000003756 stirring Methods 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- 238000010438 heat treatment Methods 0.000 claims description 16
- 239000000243 solution Substances 0.000 claims description 12
- 238000001704 evaporation Methods 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- 239000007787 solid Substances 0.000 claims description 8
- 238000001291 vacuum drying Methods 0.000 claims description 8
- 150000003242 quaternary ammonium salts Chemical class 0.000 abstract description 3
- 230000002378 acidificating effect Effects 0.000 abstract 1
- 230000003301 hydrolyzing effect Effects 0.000 abstract 1
- 238000005580 one pot reaction Methods 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 7
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 7
- 229960003237 betaine Drugs 0.000 description 7
- 239000002994 raw material Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000003863 ammonium salts Chemical class 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 229910017053 inorganic salt Inorganic materials 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000002351 wastewater Substances 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010019133 Hangover Diseases 0.000 description 1
- 102000016397 Methyltransferase Human genes 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 229940106681 chloroacetic acid Drugs 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 230000007160 gastrointestinal dysfunction Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 description 1
- 239000012022 methylating agents Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/02—Formation of carboxyl groups in compounds containing amino groups, e.g. by oxidation of amino alcohols
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/38—Separation; Purification; Stabilisation; Use of additives
- C07C227/40—Separation; Purification
- C07C227/42—Crystallisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of betaine hydrochloride, which comprises the following steps: firstly, adding chloroacetonitrile dropwise into a trimethylamine aqueous solution to form a quaternary ammonium salt intermediate, then hydrolyzing under an acidic condition, wherein the intermediate does not need to be separated and stewed in one pot, and finally obtaining a high-content and salt-free refined betaine hydrochloride product.
Description
Technical Field
The invention belongs to the technical field of feed additives, and particularly relates to a preparation method of betaine hydrochloride.
Background
Due to the structure of betaine, it can provide active methyl group, which can form methyl transferase with cysteine, participate in methyl reaction in organism metabolism, play important role in life activity, and is called as "life methylating agent".
However, because the quaternary ammonium salt and the intramolecular salt of the betaine have strong hygroscopicity, and are easy to absorb moisture in the transportation and storage processes, the use quality is influenced, so that the betaine can be generally prepared into a compound salt form, which is beneficial to transportation and storage, and can develop other effects. Among them, betaine hydrochloride is one of the most important double salt forms, and the betaine hydrochloride can better exert the efficacy of betaine due to high water solubility. Meanwhile, researches show that the betaine hydrochloride also has various pharmacological effects of promoting the regeneration of liver cells, protecting liver function, regulating gastrointestinal dysfunction, treating hangover and the like.
At present, the main preparation methods of betaine include the following methods:
one is prepared by the reaction of trimethylamine gas, chloroacetic acid and caustic soda, the method is a production method commonly applied in China at present, but a small amount of sodium chloride impurities can be introduced into the betaine prepared by the method in the purification process, and the betaine can not meet the requirements of some fields with special requirements on salt content;
the second method is to adopt trimethylamine gas and methyl chloroacetate to react in the presence of an organic solvent to obtain corresponding intermediate ammonium salt, and crack the intermediate ammonium salt at high temperature (150-250 ℃) after separation to obtain a product, wherein the reaction conditions are harsh and difficult to industrialize. Or the obtained intermediate ammonium salt is hydrolyzed to obtain a product, the method can avoid the generation of inorganic salt impurities, but the hydrolysis reaction of the ester belongs to a balanced reaction, the utilization rate of raw materials is unsatisfactory, and the use of trimethylamine gas requires pressure equipment, thereby increasing the operation difficulty;
the third method is prepared by reacting glycine and diazomethane, but since diazomethane is a gas at normal temperature and is explosive, flammable, highly toxic and highly irritant, special conditions are required for transportation, storage and use, so that the cost is high, and the method is not basically adopted at present.
On the basis of summarizing relevant experiences at home and abroad, a new route is provided, new raw materials are adopted, the conversion rate of the reaction is improved, the equipment is simple, the operation is simple and convenient, a solvent and a pressure device are not needed, the raw materials are sold in the market, the price is proper, the supply is sufficient, and the method is provided for further reducing the cost of industrial mass production of products.
Disclosure of Invention
In order to overcome the technical problems, the invention provides a preparation method of betaine hydrochloride, which comprises the following specific scheme:
a preparation method of betaine hydrochloride is characterized by comprising the following steps:
step 1: adding 1.95-2.17 parts by weight of 40% trimethylamine aqueous solution into a reactor, stirring and dropwise adding 1 part of chloroacetonitrile at room temperature, and keeping the temperature of the mixture not more than 40 ℃ in the dropwise adding process;
step 2: after the dropwise addition is finished, heating to 50-55 ℃, and continuously stirring for reaction for 2-3 hours;
and step 3: after the reaction is finished, adding 4-10 parts by weight of 20% hydrochloric acid, heating to a reflux state, and continuously stirring for reaction for 4-6 hours;
and 4, step 4: after the reaction is finished, evaporating and crystallizing the obtained betaine hydrochloride solution, filtering and collecting separated solid, and performing vacuum drying to obtain a refined betaine hydrochloride product;
the reaction formula is as follows:
compared with the prior art, the invention has outstanding substantive characteristics and remarkable progress, and particularly has the following advantages:
1. the new process method adopted by the invention has simple steps, and the generated quaternary ammonium salt intermediate can be well dissolved in water, so that the whole production process does not need to use an organic solvent, thereby reducing pollution and simultaneously reducing cost;
2. inorganic salt is not generated in the production process of the new process, the conversion efficiency of raw materials can be effectively improved by utilizing the difference of solubility, and the obtained product has better purity and yield;
3. the raw materials in each step of the method are commercially available, the source is wide, the supply is sufficient, the reaction conditions are relatively mild, the process is simple, the reactions in each step are conventional operations and are easy to control, only trace waste water is generated, the waste water can be further recycled after treatment, and the whole process is relatively compounded with the concept of green chemistry.
Detailed Description
The technical solution of the present invention will be described in detail by the following embodiments.
Example 1
Adding a 40 wt% trimethylamine aqueous solution (162.5g, about 1.1mol) into a reactor, dropwise adding chloroacetonitrile (75.5g, 1.0mol) under stirring at room temperature, keeping the temperature of the mixture not more than 40 ℃ in the dropwise adding process, heating to 50-55 ℃ after the dropwise adding is finished, continuing to stir for reaction for 3 hours, adding 20 wt% hydrochloric acid (750g) after the reaction is finished, heating to a reflux state, continuing to stir for reaction for 6 hours, evaporating most of water in the obtained betaine hydrochloride solution after the reaction is finished, crystallizing, filtering and collecting precipitated solid, and performing vacuum drying to obtain 152.1g of refined betaine hydrochloride, wherein the yield is about 99.1%.
The obtained refined betaine hydrochloride product has melting point of 227.2-228.3 deg.C (in different parts)
The solution(s),1H-NMR(d-DMSO):
δ3.29(9H,s),4.43(2H,s).MS(EI),m/z 119(M-Cl),155(M+H)。
example 2
Adding 40% by weight of trimethylamine aqueous solution (147.5g, 1.0mol) into a reactor, dropwise adding chloroacetonitrile (75.5g, 1.0mol) under stirring at room temperature, keeping the temperature of the mixture not more than 40 ℃ in the dropwise adding process, heating to 50-55 ℃ after the dropwise adding is finished, continuing to stir for reaction for 3 hours, adding 20% by weight of hydrochloric acid (230g) after the reaction is finished, heating to a reflux state, continuing to stir for reaction for 4 hours, evaporating most of water in the obtained betaine hydrochloride solution after the reaction is finished, crystallizing, filtering and collecting precipitated solid, and obtaining refined betaine hydrochloride 141.8g after vacuum drying, wherein the yield is about 92.4%.
Example 3
Adding a 40 wt% trimethylamine aqueous solution (155g, about 1.05mol) into a reactor, dropwise adding chloroacetonitrile (75.5g, 1.0mol) under stirring at room temperature, keeping the temperature of the mixture not more than 40 ℃ in the dropwise adding process, heating to 50-55 ℃ after the dropwise adding is finished, continuing to stir for reaction for 3 hours, adding 20 wt% hydrochloric acid (500g) after the reaction is finished, heating to a reflux state, continuing to stir for reaction for 5 hours, evaporating most of water in the obtained betaine hydrochloride solution after the reaction is finished, crystallizing, filtering and collecting precipitated solid, and obtaining 148.2g of refined betaine hydrochloride solution after vacuum drying, wherein the yield is about 96.5%.
Example 4
Adding 40% by weight of trimethylamine aqueous solution (147.5g, 1.0mol) into a reactor, dropwise adding chloroacetonitrile (75.5g, 1.0mol) under the condition of room temperature and stirring, keeping the temperature of the mixture not more than 40 ℃ in the dropwise adding process, heating to 50-55 ℃ after the dropwise adding is finished, continuing to stir for reaction for 3 hours, adding 20% by weight of hydrochloric acid (240g) after the reaction is finished, heating to a reflux state, continuing to stir for reaction for 4 hours, evaporating most of water in the obtained betaine hydrochloride solution after the reaction is finished, crystallizing, filtering and collecting precipitated solid, and obtaining 145.3g of refined betaine hydrochloride product after vacuum drying, wherein the yield is about 94.7%.
Example 5
Adding 40% by weight of trimethylamine aqueous solution (157.5g, about 1.07mol) into a reactor, dropwise adding chloroacetonitrile (75.5g, 1.0mol) under stirring at room temperature, keeping the temperature of the mixture not more than 40 ℃ in the dropwise adding process, heating to 50-55 ℃ after the dropwise adding is finished, continuing to stir for reaction for 2 hours, adding 20% by weight of hydrochloric acid (550g) after the reaction is finished, heating to a reflux state, continuing to stir for reaction for 5 hours, evaporating most of water in the obtained betaine hydrochloride solution after the reaction is finished, crystallizing, filtering and collecting precipitated solid, and obtaining 146.6g of refined betaine hydrochloride product after vacuum drying, wherein the yield is about 95.5%.
Example 6
Adding a 40 wt% trimethylamine aqueous solution (162.5g, about 1.1mol) into a reactor, dropwise adding chloroacetonitrile (75.5g, 1.0mol) under stirring at room temperature, keeping the temperature of the mixture not more than 40 ℃ in the dropwise adding process, heating to 50-55 ℃ after the dropwise adding is finished, continuing to stir for reaction for 3 hours, adding 20 wt% hydrochloric acid (700g) after the reaction is finished, heating to a reflux state, continuing to stir for reaction for 5 hours, evaporating most of water in the obtained betaine hydrochloride solution after the reaction is finished, crystallizing, filtering and collecting precipitated solid, and performing vacuum drying to obtain 150.7g of refined betaine hydrochloride, wherein the yield is about 98.2%.
Finally, it should be noted that: the above examples are only intended to illustrate the technical solution of the present invention and not to limit it; although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art will understand that: modifications to the specific embodiments of the invention or equivalent substitutions for parts of the technical features may be made; without departing from the spirit of the present invention, it is intended to cover all aspects of the invention as defined by the appended claims.
Claims (1)
1. A preparation method of betaine hydrochloride is characterized by comprising the following steps:
step 1: adding 1.95-2.17 parts by weight of 40% trimethylamine aqueous solution into a reactor, stirring and dropwise adding 1 part of chloroacetonitrile at room temperature, and keeping the temperature of the mixture not more than 40 ℃ in the dropwise adding process;
step 2: after the dropwise addition is finished, heating to 50-55 ℃, and continuously stirring for reaction for 2-3 hours;
and step 3: after the reaction is finished, adding 4-10 parts by weight of 20% hydrochloric acid, heating to a reflux state, and continuously stirring for reaction for 4-6 hours;
and 4, step 4: after the reaction is finished, evaporating and crystallizing the obtained betaine hydrochloride solution, filtering and collecting separated solid, and performing vacuum drying to obtain a refined betaine hydrochloride product;
the reaction formula is as follows:
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| Application Number | Priority Date | Filing Date | Title |
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| CN202111348457.8A CN113880723A (en) | 2021-11-15 | 2021-11-15 | Preparation method of betaine hydrochloride |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202111348457.8A CN113880723A (en) | 2021-11-15 | 2021-11-15 | Preparation method of betaine hydrochloride |
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20010046951A1 (en) * | 2000-02-02 | 2001-11-29 | Kao Corporation | Bleaching detergent composition |
| WO2007110162A1 (en) * | 2006-03-24 | 2007-10-04 | Clariant International Ltd | Method for producing ammonium nitriles |
| CN101823974A (en) * | 2010-05-20 | 2010-09-08 | 北京科技大学 | Preparation method by adopting (R)-(-)-glycerinchlorohydrin as chirality starting material to synthetize L-carnitine |
| CN102267918A (en) * | 2011-06-23 | 2011-12-07 | 杭州海尔希畜牧科技有限公司 | Method for preparing betaine hydrochloride |
| CN102617374A (en) * | 2011-01-31 | 2012-08-01 | 中牧实业股份有限公司 | Method for preparing betaine hydrochloride |
| CN110372525A (en) * | 2019-07-25 | 2019-10-25 | 抚顺顺能化工有限公司 | One kind synthesizing the preparation method of l-carnitine using R- (-)-epoxychloropropane as starting material |
| CN110621350A (en) * | 2017-01-06 | 2019-12-27 | 稳定技术生物制药有限公司 | Virus |
-
2021
- 2021-11-15 CN CN202111348457.8A patent/CN113880723A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20010046951A1 (en) * | 2000-02-02 | 2001-11-29 | Kao Corporation | Bleaching detergent composition |
| WO2007110162A1 (en) * | 2006-03-24 | 2007-10-04 | Clariant International Ltd | Method for producing ammonium nitriles |
| CN101823974A (en) * | 2010-05-20 | 2010-09-08 | 北京科技大学 | Preparation method by adopting (R)-(-)-glycerinchlorohydrin as chirality starting material to synthetize L-carnitine |
| CN102617374A (en) * | 2011-01-31 | 2012-08-01 | 中牧实业股份有限公司 | Method for preparing betaine hydrochloride |
| CN102267918A (en) * | 2011-06-23 | 2011-12-07 | 杭州海尔希畜牧科技有限公司 | Method for preparing betaine hydrochloride |
| CN110621350A (en) * | 2017-01-06 | 2019-12-27 | 稳定技术生物制药有限公司 | Virus |
| CN110372525A (en) * | 2019-07-25 | 2019-10-25 | 抚顺顺能化工有限公司 | One kind synthesizing the preparation method of l-carnitine using R- (-)-epoxychloropropane as starting material |
Non-Patent Citations (2)
| Title |
|---|
| NAOYA KASAI等: "AN EFFICIENT SYNTHESIS OF (R)-CARNITINE", 《TETRAHEDRON LETTERS》, vol. 33, no. 9, 31 December 1992 (1992-12-31), pages 1211 - 1212 * |
| ROBERT VOEFFRAY等: "L-Carnitine. Novel Synthesis and Determination of the Optical Purity", 《HELVETICA CHIMICA ACTA》, vol. 70, 31 December 1987 (1987-12-31), pages 2058 - 2064, XP008134586 * |
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