CN104163776A - Method for improving preparation technology of 3-(2,2-dimethylhydrazino)methyl propionate and 3-(2,2,2-trimethylhydrazino)methyl propionate - Google Patents
Method for improving preparation technology of 3-(2,2-dimethylhydrazino)methyl propionate and 3-(2,2,2-trimethylhydrazino)methyl propionate Download PDFInfo
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Abstract
The invention discloses a method for improving the preparation technology of 3-(2,2-dimethylhydrazino)methyl propionate and 3-(2,2,2-trimethylhydrazino)methyl propionate. The 3-(2,2-dimethylhydrazino)methyl propionate and 3-(2,2,2-trimethylhydrazino)methyl propionate are intermediates of a mildronate bulk drug. In the prior art, the intermediates are prepared by the following steps: making 1,1-dimehtylhydrazine carry out reactions with methyl acrylate, and then subjecting the reaction products to methylation reactions so as to obtain the target products; but the conventional technology has the disadvantages that the quality and stability of the obtain products are bad, thus the technology for producing the mildronate bulk drug becomes more complicated, and the synthesis cost is increased. The provided method separates two reactions in the synthesis route, exothermic reaction material feeding automatic control of each reaction is realized under mild conditions, the final products are subjected to a primary cooling precipitation and a secondary special purifying technology so as to obtain high purity products without complicated steps like recrystallization and washing, moreover the stability and yield of the products are both improved, the treatment time is shortened, the shelf life of the products is prolonged from two years to four years, and the method can be applied to commercial massive production.
Description
Technical field
The technology of preparing that the present invention relates to a kind of 3-(2,2 ,-dimethyl diazanyl) methyl propionate and 3-(2,2,2-trimethylammonium hydrazine) methyl propionate salt is improved one's methods, and belongs to chemosynthesis technical field.
Background technology
International generic name is Meldonium, and chemistry 3-(2,2,2-trimethylammonium hydrazine) propionate dihydrate by name is famous due to its cardioprotection.
The known method that has multiple preparation 3-(2,2,2_ trimethylammonium callosity) propionate dihydrate, generally includes:
1,1-dimethylhydrazine reacts with methyl acrylate and forms 3-(2,2-dimethyl diazanyl) methyl propionate, further with methyl halide or methyl-sulfate, generate corresponding 3-(2,2,2-trimethylammonium hydrazine) methyl propionate halogenide or methyl sulfate, then it is hydrolyzed and deionization, separated with the saturated solution of carbonic acid gas or sulfurous gas, in ethanol, to carry out obtaining dihydrate inner salt after crystallization. this ordinary method avoids using electrodialysis, and has a lot of shortcomings: strong basic ion exchange resin is unstable and be decomposed or be oxidized in treating processes; Strong basic ion exchange resin only bears the reprocessing cycle of limited number of time; Resin regeneration needs a large amount of solvents, bronsted lowry acids and bases bronsted lowry and deionized water; Therefore and ion-exchange capacity is low, use this method to prepare the production cost of 3-(2,2,2-trimethylammonium hydrazine) propionate dihydrate generally very high.
Yet meanwhile, acquisition is also extremely important for the production of the method for the high quality Meldonium bulk drug intermediate of 3-(2,2,2-trimethylammonium hydrazine) propionate dihydrate.3-(2,2,2-trimethylammonium hydrazine) methyl propionate salt is one of this type of intermediate.The ordinary method of producing this intermediate is to make 1, 1-dimethylhydrazine reacts with methyl acrylate and then obtains target product with methylating reagent halide reaction, the method of this conventional continuity reaction has a lot of shortcomings: by product and oxide impurity that 1) the first step reaction generates are directly brought into second step reaction, on the one hand a lot of by products are methylated and form the second month in a season by methylating reagent equally, uncle or quaternary ammonium salt cause in target crude product foreign matter content and kind complicated, the 3-(2 finally obtaining, 2, 2-trimethylammonium hydrazine) color of methyl propionate salt is very dark, cause certain difficulty to aftertreatment purifying, increase production cost, the more important thing is direct quality and the stability that affects productive rate and product, such as current 3-(2, 2, 2-trimethylammonium hydrazine) international quality standards of methyl propionate bromide: outward appearance is white, faint yellow or pink crystalline powder, fusing point is 118-135 ℃, main content 99.5-105%, valid until 2 years.2) reaction of this continuity is difficult to the correct response proportionlity of the each reactant of prediction and intermediate, makes quality product, output and the production technique cannot stabilization.3) react raw material easily polymerization or oxidizable at a certain temperature used, although go up according to a conventional method the oxidation that stops raw material and intermediate by the method for nitrogen air-isolation, but related temperature of reaction and pressure can accelerate alkylated reaction, Ren Ranhui causes the generation of a large amount of by products.4) for Na. Qi Kanei, Mali this. the public announcement of a patent application CN102036949A of this invention of Ewald Tilker has and openly mentions the method that adds antioxidant in reactant, although this method suppresses the generation of part by product, but also thoroughly do not solve the complete optimization and stability of the finished product technique, the antioxidant that adds is residual to be had a certain impact to bulk drug tool, and therefore this method does not also obtain the license of pharmacopeia in industrial production.
Summary of the invention:
In conventional synthetic method, 1,1-dimethylhydrazine with methyl acrylate in the situation that react set comparatively high temps and higher reaction pressure reaction generates several by products.In addition 1, the oxidizable oxide compound that may form of 1-dimethylhydrazine itself has 1-18, and as Fig. 1, this oxide compound some and methyl acrylate are reacted into different types of by product.Such as forming dimethyl amine in 1,1-dimethylhydrazine oxidation, react formation by product 3-(dimethylamino) methyl propionate with methyl acrylate, also can the interact a kind of reaction system of complexity of the different higher-boiling compounds of formation of other oxide compound.Similarly, methyl acrylate polymerization reaction take place or product 3-(2,2-dimethyl diazanyl) methyl propionate under this reaction conditions waited a moment and is oxidized to slowly 2-(2,2-dimethyl hydrazone group) methyl acetate etc. air-sensitive.Generally speaking the by product kind of the first step reaction is more various than more complicated, if by product increases the quality that causes Meldonium intermediate target product to be difficult to purify and directly affect Meldonium bulk drug when we carry out methylation reaction in reaction system in this doublely.
The technical problem to be solved in the present invention is to overcome the problem that above-mentioned prior art exists, invented a kind of 3-(2, 2,-dimethyl diazanyl) methyl propionate and 3-(2, 2, 2-trimethylammonium hydrazine) the halid technology of preparing of methyl propionate is improved one's methods, the feature of this method is: with 1, 1-dimethylhydrazine and methyl acrylate are starting raw material, adopt the synthetic route different from forefathers, be exactly that addition reaction and methylation reaction carry out as two kinds of independent building-up reactions steps, concrete steps are as follows: 1) the first step reaction is a kind of thermopositive reaction, therefore, in order to make stable rising of temperature of reaction, control better the by-products content in reaction, on synthesis technique, set a kind of with feeding quantity, temperature, the best curve figure in pressure and reaction times is as standard, having realized the automatization of a whole set of reaction controls.2) reaction finishes a kind of accurate filter of rear use cooling good intermediate is filtered to purifying.3) intermediate by detect the qualified rear starting raw material as methylation reaction again accurate-metering feed intake.4) methylation reaction is also thermopositive reaction, in order to make stable rising of temperature of reaction control better by-products content in reaction and set equally a kind of best curve figure of usining feeding quantity, temperature, pressure and reaction times as standard on synthesis technique, realized the automatization of a whole set of reaction and controlled.5) adopted a kind of method of special purification technique, it can make the crude product after methylation reaction finishes carry out the complicated purge processes such as recrystallization washing after conventional filtration, can directly take sterling.Main advantage of the present invention is 3-(2,2,-dimethyl diazanyl) methyl propionate intermediate can lot production store the starting raw material as second step reaction completely, greatly reduced so a whole set of reaction time used, the more important thing is the stability and the quality product that have guaranteed production technique, can high yield change into target product.The second advantage is that the high purity product that the finished product not only can directly obtain without complex processes such as recrystallization, washings has also improved product stability and productive rate, the quality guaranteed period of product according to a conventional method within 2 years, extend to 4 years, realized business scale operation, reduced costs, the advantage such as equipment is simple to operation.
Chemical equation is as follows:
1)CH
2＝CH-COOCH
3+(CH
3)
2N-NH
2→(CH
3)
2N-NH-CH
2-CH
2-COOCH
3
Side reaction:
2)(CH
3)
2N-NH-CH
2-CH
2-COOCH
3+CH
3X→(CH
3)
3N
+-NH-CH
2-CH
2-COOCH
3
X
-
Side reaction:
1. moiety: Meldonium bulk drug intermediate 3-(2,2,2-trimethylammonium hydrazine) the halid molecular formula of methyl propionate is: (CH
3)
3n
+nHCH
2cH
2cOOCH
3x
-, wherein, X represents Cl
-, Br
-, I
-, CH
3sO
4 --; The molecular formula of intermediate product 3-(2,2 ,-dimethyl diazanyl) methyl propionate is: (CH
3)
2n-NH-CH
2-CH
2-COOCH
3; Methylating reagent is a kind of in methyl chloride, monobromethane, methyl iodide, methyl-sulfate or methylcarbonate.
2. component proportions:
In step 1:
The methyl acrylate of described dropping excess molar ratio 1-50%, refers to and drips methyl acrylate to excessive, the mol ratio of excessive methyl acrylate and 1,1-dimethylhydrazine is 1-50%.
In step 2:
The methylating reagent of described dropping excess molar ratio 1-20%, refers to and drips methylating reagent to excessive, the mol ratio of excessive methylating reagent and 3-(2,2 ,-dimethyl diazanyl) methyl propionate is 5-30%.
Described methylating reagent is selected from a kind of in halogenated alkane, methyl-sulfate or methylcarbonate; Described alcoholic solvent is selected from a kind of in lower alcohol ethanol, methyl alcohol, ethylene glycol, propylene glycol or other alcohol compounds.
3. technique:
A; The synthesis technique of 3-(2,2 ,-dimethyl diazanyl) methyl propionate
1) addition reaction: 1,1-dimethylhydrazine is dripped to methyl acrylate and constantly stirs;
2) sampling detects and determines whether addition reaction stops;
3) vacuum distilling;
4) cooling precipitation;
5) secondary filter;
6) packing: air-isolation, nitrogen protection all the time store.
B; The synthesis technique of 3-(2,2,2-trimethylammonium hydrazine) methyl propionate salt
1) methylate: the alcoholic solution of 3-(2,2 ,-dimethyl diazanyl) methyl propionate is methylated by excessive methylating reagent;
2) purifying
3) suction filtration
4) vacuum-drying: crystallinity white powder, vacuum-drying at 20-110 ℃;
5) packing: bulk drug packaging HDPE (low-pressure high-density polyethylene) material, two-layer bag (
60*80cm), every layer of bag all must seal separately, and outsourcing is the special-purpose fiber can of bulk drug, with wax, seals.Every barrel of net weight 25kg (standard).Packing specifications:
36*40cm; Transportation: according to OST64-034-87; Store: lucifuge, dry place; Through long-term stable experiment, determine that the storage life is 4 years.
Technical process A is: addition reaction-vacuum distilling-cooling precipitation-secondary filter-packing.
Process flow B is: methylate-purifying-suction filtration-vacuum distilling-vacuum-drying-packing.
Technique effect
The technology of the present invention effect is that 3-(2,2 ,-dimethyl diazanyl) the methyl propionate intermediate that adopts above-mentioned technique to obtain is a kind of colourless transparent liquid, product content >=98.5%; Meldonium bulk drug intermediate 3-(2,2,2-trimethylammonium hydrazine) the main content of methyl propionate halogenide product is controlled between 100.0-102.0%, it is a kind of white crystalline powder, 3-(2,2,2-trimethylammonium hydrazine) melting range of methyl propionate bromine salt is: 126-132 ℃, keeping life is 4 years.Adopt this technique not only to guarantee quality product and improved its stability, it is a kind of white crystalline powder, also keeping life was put off until to 4 years by original 2 years, realized business scale operation, reduced costs, technique is simple, high yield, by complex processes such as recrystallization, washings, can directly not obtain highly purified bulk drug intermediate, the more important thing is to have solved and prepare Meldonium 3-(2,2,2_ trimethylammonium hydrazine) problem of aftertreatment difficulty has also reduced cost during propionate dihydrate.
Accompanying drawing explanation
Fig. 1 is the oxidizable oxide compound that may form of 1,1-dimethylhydrazine itself.
Embodiment
Below with reference to following indefiniteness embodiment, the present invention is described in more detail, first three plants embodiment is that after original technique, three kinds of embodiment are the result comparison improving after technique.
Embodiment 1
In the three neck round-bottomed flasks with tool agitator, dropping funnel and reflux exchanger, add methyl acrylate 172g (2mol), under cooling, drip 1 of 132g (2.2mol), 1-dimethylhydrazine, time 2 h drips off, subsequently reaction mixture is heated until form 3-(2,2_ dimethyl diazanyl) methyl propionate (monitoring by GM-MS) in equality of temperature.
By above-mentioned 3-(2,2_ dimethyl diazanyl) methyl propionate product is dissolved in 40% ethanol (350ml), be cooled to 0 ℃, pass into monobromethane (189g, 1.99mol) the 1 hour time, continue equality of temperature and stir 0,5 hour, cold filtration is yellow or brown throw out partially, utilizes acetone (1000ml) washing crude product.Be dried to obtain yellow 3-(2,2,2_ trimethylammonium hydrazine) methyl propionate bromide crude product 265.7g, yield 91.0%; Ethyl alcohol recrystallization, the dry light yellow crystalline powder 219.8g that obtains for crude product, productive rate 75.3%, fusing point 130-132 ℃, main content 103.3% (is verified by stability experiment, less stable, color progressively deepens, because contained trace impurity is larger on product impact, discovery has molecular formula decay, each index changes greatly, and keeping life mostly is 2 years most).
Embodiment 2
Repeat synthetic rear dry brown color 3-(2,2,2_ trimethylammonium hydrazine) the methyl propionate bromide crude product 261.3g of obtaining of method in above-described embodiment 1, yield 89.5%; Ethyl alcohol recrystallization, the dry white crystalline powder 214.2g that obtains for crude product, productive rate 73.4%, fusing point 133-135 ℃, main content 102.5% (is verified by stability experiment, less stable, color progressively deepens, because contained trace impurity is larger on product impact, discovery has molecular formula decay, each index changes greatly, and keeping life mostly is 2 years most).
Embodiment 3
Repeat synthetic rear dry faint yellow 3-(2,2,2_ trimethylammonium hydrazine) the methyl propionate bromide crude product 271.5g of obtaining of method in above-described embodiment 1, yield 89.5%; Ethyl alcohol recrystallization, the dry white crystalline powder 225.3g that obtains for crude product, productive rate 77.2%, fusing point 132-134 ℃, main content 103.0% (is verified by stability experiment, less stable, color progressively deepens, because contained trace impurity is larger on product impact, discovery has molecular formula decay, each index changes greatly, and keeping life mostly is 2 years most).
Embodiment 4
With tool agitator, in three neck round-bottomed flasks of dropping funnel and reflux exchanger, add methyl acrylate 258g (3mol), under cooling, drip 1 of 192g (3.2mol), 1-dimethylhydrazine, time 2 h drips off, subsequently reaction mixture is heated in equality of temperature until form 3-(2, 2_ dimethyl diazanyl) methyl propionate (monitoring by GM-MS), cooling static the spending the night of nitrogen protection pressurization found part viscous material precipitation, with the sticky shape throw out of secondary filter filtering, obtain 3-(2, 2_ dimethyl diazanyl) methyl propionate colourless transparent liquid (417g, productive rate 95.2%, content is 99.2%) (with dark place in the container of air-isolation, preserve, minute third-order reaction is standby).
By above-mentioned 3-(2, 2_ dimethyl diazanyl) methyl propionate (139g, 0.95mol) be dissolved in 40% ethanol (350ml), be cooled to 0 ℃, pass into monobromethane (123g, 1.30mol), 1 hour time, continue equality of temperature and stir O, 5 hours, the throw out of cold filtration white, a small amount of cold alcohol solvent washs and washes on strainer, mother liquor obtains white crystalline powder 3-(2 by being dried after draining, 2, 2_ trimethylammonium hydrazine) methyl propionate bromide sterling 212, 4g, main content is 100.4%, productive rate is 94.4%, fusing point is 129-130 ℃ and (by stability experiment, verifies, stability is better, product colour does not become, contained trace impurity type is little on product impact, by the stability tests of 4 years, find to have molecular formula decay small, the proterties of sample, fusing point, the indexs such as content meet pharmacopeia relevant regulations, stable performance, long-term storage is never degenerated, the complete conformance with standard of quality, keeping life can extend to 4 years).
Embodiment 5
Direct cold filtration after the method that repeats in above-described embodiment 4 is synthetic, the dry white crystalline powder 3-(2 that obtains, 2, 2_ trimethylammonium hydrazine) methyl propionate bromide sterling 211.5g, main content is 100.8%, productive rate is 94.0%, fusing point is 130-131 ℃ and (by stability experiment, verifies, stability is better, product colour does not become, contained trace impurity type is little on product impact, by the stability tests of 4 years, find to have molecular formula decay small, the proterties of sample, fusing point, the indexs such as content meet pharmacopeia relevant regulations, stable performance, long-term storage is never degenerated, the complete conformance with standard of quality, keeping life can extend to 4 years).
Embodiment 6
Direct cold filtration after the method that repeats in above-described embodiment 4 is synthetic, the dry white crystalline powder 3-(2 that obtains, 2, 2_ trimethylammonium hydrazine) methyl propionate bromide sterling 214.0g, main content is 100.3%, productive rate is 95.1%, fusing point is 129-130 ℃ and (by stability experiment, verifies, stability is better, product colour does not become, contained trace impurity type is little on product impact, by the stability tests of 4 years, find to have molecular formula decay small, the proterties of sample, fusing point, the indexs such as content meet pharmacopeia relevant regulations, stable performance, long-term storage is never degenerated, the complete conformance with standard of quality, keeping life can extend to 4 years).
Claims (3)
1. a 3-(2,2 ,-dimethyl diazanyl) methyl propionate and 3-(2,2,2-trimethylammonium hydrazine) technology of preparing of methyl propionate salt is improved one's methods, and it is characterized in that: Meldonium bulk drug intermediate 3-(2,2,2-trimethylammonium hydrazine) molecular formula of methyl propionate salt is: (CH
3)
3n
+nHCH
2cH
2cOOCH
3x
-, wherein, X represents Cl
-, Br
-, I
-, CH
3sO
4 --; The molecular formula of intermediate product 3-(2,2 ,-dimethyl diazanyl) methyl propionate is: (CH
3)
2n-NH-CH
2-CH
2-COOCH
3; Methylating reagent is a kind of in methyl chloride, monobromethane, methyl iodide, methyl-sulfate or methylcarbonate.
Technique is included as:
A; The synthesis technique of 3-(2,2 ,-dimethyl diazanyl) methyl propionate
B; The synthesis technique of 3-(2,2,2-trimethylammonium hydrazine) methyl propionate salt.
2. a kind of 3-(2 according to claim 1, 2,-dimethyl diazanyl) methyl propionate and 3-(2, 2, 2-trimethylammonium hydrazine) technology of preparing of methyl propionate salt is improved one's methods, it is characterized in that: the synthetic route that we change forefathers is exactly that addition reaction and methylation reaction carry out as two kinds of independent building-up reactions steps, concrete steps are as follows: 1) the first step reaction is a kind of thermopositive reaction, therefore, in order to make stable rising of temperature of reaction, control better the by-products content in reaction, on synthesis technique, set a kind of with feeding quantity, temperature, the best curve figure in pressure and reaction times is as standard, having realized the automatization of a whole set of reaction controls.2) reaction finishes a kind of accurate filter of rear use cooling good intermediate is filtered to purifying.3) intermediate by detect the qualified rear starting raw material as methylation reaction again accurate-metering feed intake.4) methylation reaction is also thermopositive reaction, in order to make stable rising of temperature of reaction control better by-products content in reaction and set equally a kind of best curve figure of usining feeding quantity, temperature, pressure and reaction times as standard on synthesis technique, realized the automatization of a whole set of reaction and controlled.5) adopted a kind of method of special purification technique, it can make the crude product after methylation reaction finishes carry out the complicated purge processes such as recrystallization washing after conventional filtration, can directly take sterling.Desalination technology after carbonic acid gas or SO 2 acidifying or the synthetic technology scheme of utilizing first relevant ammonium salt acidifying must synthesize Meldonium bulk drug.
3. a kind of 3-(2 according to claim 1,2,-dimethyl diazanyl) methyl propionate and 3-(2,2,2-trimethylammonium hydrazine) technology of preparing of methyl propionate salt is improved one's methods, and it is characterized in that 3-(2,2,-dimethyl diazanyl) methyl propionate intermediate is a kind of colourless transparent liquid, product content >=98.5%; Meldonium bulk drug intermediate 3-(2,2,2-trimethylammonium hydrazine) the main content of methyl propionate product salt is between 100.0-102.0%, be-kind of white crystalline powder, 3-(2,2,2-trimethylammonium hydrazine) melting range of methyl propionate bromine salt is: 126-132 ℃, shelf life of products is 4 years.
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| CN201410161546.5A CN104163776A (en) | 2014-05-28 | 2014-05-28 | Method for improving preparation technology of 3-(2,2-dimethylhydrazino)methyl propionate and 3-(2,2,2-trimethylhydrazino)methyl propionate |
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| CN201410161546.5A CN104163776A (en) | 2014-05-28 | 2014-05-28 | Method for improving preparation technology of 3-(2,2-dimethylhydrazino)methyl propionate and 3-(2,2,2-trimethylhydrazino)methyl propionate |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109369447A (en) * | 2018-11-05 | 2019-02-22 | 东力（南通）化工有限公司 | Improved method of preparation technology of 3- (2, 2, 2-trimethylhydrazinium) propionate dihydrate |
| CN111333534A (en) * | 2019-12-13 | 2020-06-26 | 东力（南通）化工有限公司 | Novel method for preparing 3- (2, 2, 2-trimethylhydrazinium) propionate dihydrate by methyl methylation of methyl halide |
| CN115197092A (en) * | 2021-04-13 | 2022-10-18 | 东力（南通）化工有限公司 | Preparation method for converting alkyl hydrazine methyl propionate industrial waste into veterinary bulk drug |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| LT5598B (en) * | 2006-09-04 | 2009-10-26 | Jorge Silva | Method for producing 3-(2,2,2-trimethylhydrazinium)propionate dihydrate |
| CN101973909A (en) * | 2010-11-19 | 2011-02-16 | 绍兴文理学院 | Preparation method of mildronate |
| CN104151192A (en) * | 2014-05-07 | 2014-11-19 | 东力（南通）化工有限公司 | Improved method of preparation technology of mildronate intermediate 3-(2,2,2-trimethylhydrazine) methyl acrylate methyl sulfate |
-
2014
- 2014-05-28 CN CN201410161546.5A patent/CN104163776A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| LT5598B (en) * | 2006-09-04 | 2009-10-26 | Jorge Silva | Method for producing 3-(2,2,2-trimethylhydrazinium)propionate dihydrate |
| CN101973909A (en) * | 2010-11-19 | 2011-02-16 | 绍兴文理学院 | Preparation method of mildronate |
| CN104151192A (en) * | 2014-05-07 | 2014-11-19 | 东力（南通）化工有限公司 | Improved method of preparation technology of mildronate intermediate 3-(2,2,2-trimethylhydrazine) methyl acrylate methyl sulfate |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109369447A (en) * | 2018-11-05 | 2019-02-22 | 东力（南通）化工有限公司 | Improved method of preparation technology of 3- (2, 2, 2-trimethylhydrazinium) propionate dihydrate |
| CN109369447B (en) * | 2018-11-05 | 2022-05-13 | 东力（南通）化工有限公司 | Improved method of preparation technology of 3- (2, 2, 2-trimethylhydrazinium) propionate dihydrate |
| CN111333534A (en) * | 2019-12-13 | 2020-06-26 | 东力（南通）化工有限公司 | Novel method for preparing 3- (2, 2, 2-trimethylhydrazinium) propionate dihydrate by methyl methylation of methyl halide |
| CN111333534B (en) * | 2019-12-13 | 2022-06-28 | 东力（南通）化工有限公司 | Method for preparing 3- (2, 2, 2-trimethylhydrazinium) propionate dihydrate by methylating methyl halide |
| CN115197092A (en) * | 2021-04-13 | 2022-10-18 | 东力（南通）化工有限公司 | Preparation method for converting alkyl hydrazine methyl propionate industrial waste into veterinary bulk drug |
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Application publication date: 20141126 |
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