CN106977411B - Synthetic method of N-methyltyramine hydrochloride - Google Patents
Synthetic method of N-methyltyramine hydrochloride Download PDFInfo
- Publication number
- CN106977411B CN106977411B CN201710156217.5A CN201710156217A CN106977411B CN 106977411 B CN106977411 B CN 106977411B CN 201710156217 A CN201710156217 A CN 201710156217A CN 106977411 B CN106977411 B CN 106977411B
- Authority
- CN
- China
- Prior art keywords
- reaction
- stirring
- hydrochloride
- methyltyramine
- solvent
- 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.)
- Expired - Fee Related
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
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a synthetic method of N-methyltyramine hydrochloride, belonging to the technical field of organic synthesis. Which comprises the following steps: dissolving p-hydroxyphenylacetic acid in a first solvent, adding thionyl chloride, refluxing and stirring until the reaction is complete, cooling, dripping the reaction solution into a methylamine aqueous solution, keeping the temperature and stirring after dripping, and filtering to obtain an intermediate; dissolving the intermediate in a second solvent, adding a reducing agent at room temperature, then adding Lewis acid in batches, heating, refluxing and stirring overnight, introducing the reaction solution into an acid solution after the reaction is finished, then adjusting the pH to be neutral, filtering and separating liquid after stirring, introducing hydrogen chloride gas into the second solvent layer until the hydrogen chloride gas is saturated and the pH of the solution is 1, stirring, then performing suction filtration, leaching the solid, and drying to obtain the N-methyl tyramine hydrochloride. The method has the advantages of mild reaction conditions, high conversion rate, cheap and easily-obtained raw materials, low synthesis cost because the used reagents are cheap conventional reagents, simple and feasible post-treatment, no generation of a large amount of three wastes, high product yield and purity and good quality.
Description
Technical Field
The invention relates to a synthetic method of an organic synthetic intermediate, in particular to a synthetic method of N-methyltyramine hydrochloride, belonging to the technical field of organic synthesis.
Background
N-methyltyramine hydrochloride having the formula:
the N-methyltyramine hydrochloride is white prismatic crystal (ethanol), flaky crystal (benzene), has a melting point of 130-131 ℃ and a boiling point of 183-185 ℃ (1.20kPa) and is slightly soluble in water, and the raw materials mainly come from plant extraction, dried young fruits of a rutaceae plant Citrus aurantium, Peganum microphyllum of Cactaceae, and roots of leguminous plant Desmodium hirsutum. Has effects in promoting metabolism, inhibiting bacterial growth, and can be widely used as antiseptic for food or cosmetic and as industrial antibacterial.
The literature related to N-methyltyramine hydrochloride in the prior art is Chinese patent application document (publication number: CN103755576A) which discloses a method for synthesizing N-methyltyramine hydrochloride, and the method specifically disclosed in the patent is
The method adopts methylamino acetonitrile hydrochloride as a raw material, and obtains the N-methyl tyramine hydrochloride by palladium-carbon reduction, wherein the methylamino acetonitrile hydrochloride is purchased from thousands of yuan per kilogram, a noble metal catalyst palladium-carbon is needed for reduction, the cost is extremely high, the equipment loss and the post-treatment cost are extremely high, and the yield of the method is only about 64 percent.
In addition, the prior art also adopts methylamino acetonitrile hydrochloride as a raw material to synthesize the N-methyl tyramine hydrochloride by reaction, but the danger is classified as 35/36/37, the N-methyl tyramine hydrochloride has sensitization on eyes and soft tissues, and the N-methyl tyramine hydrochloride has great harm to the environment and operators.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides the synthesis method of the N-methyltyramine hydrochloride, which has the advantages of simple method, low cost and high yield.
The invention aims to provide a method for synthesizing N-methyltyramine hydrochloride, which comprises the following steps:
condensation reaction: dissolving p-hydroxyphenylacetic acid in a first solvent, adding thionyl chloride, refluxing and stirring until the reaction is complete, cooling, dripping the reaction solution into a methylamine aqueous solution, keeping the temperature and stirring after dripping, and filtering to obtain an intermediate;
reduction reaction: dissolving the intermediate in a second solvent, adding a reducing agent at room temperature, then adding Lewis acid in batches, heating, refluxing and stirring overnight, introducing the reaction solution into an acid solution after the reaction is finished, then adjusting the pH to be neutral, filtering and separating liquid after stirring, introducing hydrogen chloride gas into the second solvent layer until the hydrogen chloride gas is saturated and the pH of the solution is 1, stirring, then performing suction filtration, leaching the solid, and drying to obtain the N-methyl tyramine hydrochloride.
The invention uses p-hydroxyphenylacetic acid to form acyl chloride through thionyl chloride, then uses methylamine to replace the acyl chloride to obtain an intermediate, and then uses the intermediate to obtain a target product through catalytic reduction. The synthesis method has simple and feasible post-treatment, does not generate a large amount of three wastes, and has higher yield.
In the method for synthesizing the N-methyltyramine hydrochloride, the mass ratio of the p-hydroxyphenylacetic acid to the thionyl chloride in the condensation reaction is 1: 0.8-1.5. If the mass ratio of the p-hydroxyphenylacetic acid to the thionyl chloride is too large, the thionyl chloride is less and the reaction is incomplete; on the other hand, if the ratio is small, the thionyl chloride is excessively excessive, and the post-treatment for removing the excessive thionyl chloride is time-consuming and costly.
In the method for synthesizing the N-methyltyramine hydrochloride, the solvent of methylamine water in the condensation reaction is 40%. In the method for synthesizing the N-methyltyramine hydrochloride, the temperature for adding the thionyl chloride in the condensation reaction is-5 ℃. If thionyl chloride is added at a temperature higher than 5 ℃, the reaction is easy to wash, and if thionyl chloride is added at a temperature lower than-5 ℃, the reaction is slow, thereby affecting the efficiency of the whole synthesis reaction. In the synthesis method of the N-methyltyramine hydrochloride, the first solvent in the condensation reaction is one or more of dichloromethane, trichloromethane, tetrahydrofuran, acetone, butanone and toluene. Preferably, the first solvent is dichloromethane.
In the synthesis method of the N-methyltyramine hydrochloride, the reducing agent in the reduction reaction is one or two of sodium borohydride and potassium borohydride.
In the synthesis method of the N-methyltyramine hydrochloride, the Lewis acid in the reduction reaction is one or more of aluminum trichloride, zinc chloride, lithium chloride, calcium chloride and ferric trichloride. The Lewis acid is matched with sodium borohydride for use, so that the reduction effect of the sodium borohydride is reduced, and the reduction reaction is milder. If the Lewis acid is not contained in the method, the reaction is incomplete, the selectivity is poor, byproducts are easily generated, and the yield is seriously influenced.
In the method for synthesizing the N-methyltyramine hydrochloride, the mass ratio of the reducing agent to the Lewis acid in the reduction reaction is 1: 0.4-1.2. If the proportion is too large, the Lewis acid is less, so that incomplete reaction can be caused; too small a proportion of Lewis acid increases the time and cost of the post-treatment.
In the synthesis method of the N-methyltyramine hydrochloride, the solvent II in the reduction reaction is one or more of methyl tert-butyl ether, toluene, ethyl acetate, tetrahydrofuran and ethylene glycol dimethyl ether. Preferably, the second solvent is tetrahydrofuran.
In the invention, the solvent I is selected from a solvent which can dissolve p-hydroxyphenylacetic acid and does not react with thionyl chloride, and is preferably dichloromethane, because dichloromethane has low boiling point and high polarity, raw materials and products are dissolved in dichloromethane, and the reaction process and speed are accelerated. The second solvent is selected from a solvent which can dissolve the first intermediate and does not react with the reducing agent and the Lewis acid, and meanwhile, the solvent with high yield in the step of forming the hydrochloride is preferably tetrahydrofuran which has small polarity, has complexation effect on the reducing agent and the Lewis acid and is superior to other selected solvents.
The chemical reaction formula of the synthetic method is as follows:
in summary, the invention has the following advantages:
1. the method for synthesizing the N-methyltyramine hydrochloride has the advantages of low-cost and easily-obtained raw materials, low-cost reagents which are conventional reagents, low synthesis cost, simple and easy post-treatment and no generation of a large amount of three wastes.
2. The method for synthesizing the N-methyltyramine hydrochloride has the advantages of mild reaction conditions, high conversion rate, high yield and purity of the finally obtained product N-methyltyramine hydrochloride and good product quality.
Drawings
FIG. 1 is a liquid chromatogram of N-methyltyramine hydrochloride synthesized by the method of the invention.
Detailed Description
The following are specific embodiments of the present invention and are further described with reference to the drawings, but the present invention is not limited to these embodiments.
Example 1
Condensation reaction: 153g of p-hydroxyphenylacetic acid is dissolved in 200mL of dichloromethane, 120g of thionyl chloride is dripped at 0 ℃, reflux stirring is carried out for 5 hours until TLC detection reaction is finished, the mixture is dripped into 800mL of 40% methylamine water solution after cooling, heat preservation stirring is carried out for 2 hours after dripping is finished, suction filtration is carried out, and filter cakes are leached by water to obtain 150g of yellow solid intermediate;
reduction reaction: adding 1000mL of tetrahydrofuran into a 10L reaction bottle, adding the intermediate, adding 76g of sodium borohydride at room temperature, adding 133g of aluminum trichloride in batches, and refluxing and stirring overnight after the completion. After TLC detection reaction is finished, slowly pouring the reaction liquid into 2000mL of 6mol/L diluted hydrochloric acid, stirring for 1 hour, dropwise adding an aqueous sodium hydroxide solution until the pH value is 7, stirring for 1 hour, filtering, separating liquid, introducing hydrogen chloride gas into a dried tetrahydrofuran layer until the solution pH value is 1, precipitating a large amount of white solid, stirring for 1 hour at 0 ℃, suction-filtering, leaching the solid with cooled 500mL ethyl acetate once, and drying at 60 ℃ to obtain 160g of N-methyltyramine hydrochloride product, wherein the yield is 91% and the purity is 99.9%.
Example 2
Condensation reaction: dissolving 76.5g of p-hydroxyphenylacetic acid in 100mL of acetone, dripping 90g of thionyl chloride at 0 ℃, refluxing and stirring for 5 hours until TLC detection reaction is finished, dripping into 400mL of 40% methylamine aqueous solution after cooling, keeping the temperature and stirring for 2 hours after dripping, carrying out suction filtration, and leaching a filter cake with water to obtain 75g of a yellow solid intermediate;
reduction reaction: 500mL of toluene was added to a 5.0L reaction flask, the intermediate was added, 38g of sodium borohydride was added at room temperature, 66.5g of aluminum trichloride was added in portions, and after completion, the mixture was refluxed and stirred overnight. After TLC detection reaction is finished, slowly pouring the reaction liquid into 1000mL of 6mol/L diluted hydrochloric acid, stirring for 1 hour, dropwise adding a sodium hydroxide aqueous solution until the pH value is 7, stirring for 1 hour, filtering, separating liquid, introducing hydrogen chloride gas into a dried tetrahydrofuran layer until the solution pH value is 1, precipitating a large amount of white solid, stirring for 1 hour at 0 ℃, suction-filtering, leaching the solid with cooled 300mL ethyl acetate once, and drying at 60 ℃ to obtain 78g of N-methyltyramine hydrochloride product, wherein the yield is 89%, and the purity is 99.1%.
Example 3
Condensation reaction: 153g of p-hydroxyphenylacetic acid is dissolved in 200mL of trichloromethane, 120g of thionyl chloride is dripped at 0 ℃, the mixture is refluxed and stirred for 5 hours until TLC detection reaction is finished, the mixture is dripped into 800mL of 40% methylamine water solution after cooling, the mixture is stirred for 2 hours under heat preservation after dripping, suction filtration is carried out, and filter cakes are leached by water to obtain 150g of yellow solid intermediate;
reduction reaction: 1000mL of tetrahydrofuran is added into a 10L reaction bottle, the intermediate is added, 76g of sodium borohydride is added at room temperature, 266g of aluminum trichloride is added in batches, and after the completion, reflux stirring is carried out overnight. After TLC detection reaction is finished, slowly pouring the reaction liquid into 2000mL of 6mol/L diluted hydrochloric acid, stirring for 1 hour, dropwise adding an aqueous sodium hydroxide solution until the pH value is 7, stirring for 1 hour, filtering, separating liquid, introducing hydrogen chloride gas into a dried tetrahydrofuran layer until the solution pH value is 1, precipitating a large amount of white solid, stirring for 1 hour at 0 ℃, suction-filtering, leaching the solid with cooled 500mL ethyl acetate once, and drying at 60 ℃ to obtain 160g of N-methyltyramine hydrochloride product, wherein the yield is 91% and the purity is 99.7%.
Example 4
Condensation reaction: 153g of p-hydroxyphenylacetic acid is dissolved in 200mL of trichloromethane, 120g of thionyl chloride is dripped at 0 ℃, the mixture is refluxed and stirred for 5 hours until TLC detection reaction is finished, the mixture is dripped into 800mL of 40% methylamine water solution after cooling, the mixture is stirred for 2 hours under heat preservation after dripping, suction filtration is carried out, and filter cakes are leached by water to obtain 150g of yellow solid intermediate;
reduction reaction: 1000mL of tetrahydrofuran is added into a 10L reaction bottle, the intermediate is added, 76g of potassium borohydride is added at room temperature, 266g of ferric chloride is added in batches, and after the completion, reflux stirring is carried out overnight. After TLC detection reaction is finished, slowly pouring the reaction liquid into 2000mL of 6mol/L diluted hydrochloric acid, stirring for 1 hour, dropwise adding an aqueous sodium hydroxide solution until the pH value is 7, stirring for 1 hour, filtering, separating liquid, introducing hydrogen chloride gas into a dried tetrahydrofuran layer until the solution pH value is 1, precipitating a large amount of white solid, stirring for 1 hour at 0 ℃, suction filtering, leaching the solid with cooled 500mL ethyl acetate once, and drying at 60 ℃ to obtain 167g of N-methyltyramine hydrochloride product, wherein the yield is 95% and the purity is 99.4%.
Example 5
Condensation reaction: 153g of p-hydroxyphenylacetic acid is dissolved in 200mL of trichloromethane, 120g of thionyl chloride is dripped at 0 ℃, the mixture is refluxed and stirred for 5 hours until TLC detection reaction is finished, the mixture is dripped into 800mL of 40% methylamine water solution after cooling, the mixture is stirred for 2 hours under heat preservation after dripping, suction filtration is carried out, and filter cakes are leached by water to obtain 150g of yellow solid intermediate;
reduction reaction: 1000mL of tetrahydrofuran is added into a 10L reaction bottle, the intermediate is added, 76g of sodium borohydride is added at room temperature, 222g of calcium chloride is added in batches, and after the completion, reflux stirring is carried out overnight. After TLC detection reaction is finished, slowly pouring the reaction liquid into 2000mL of 6mol/L diluted hydrochloric acid, stirring for 1 hour, dropwise adding an aqueous sodium hydroxide solution until the pH value is 7, stirring for 1 hour, filtering, separating liquid, introducing hydrogen chloride gas into a dried tetrahydrofuran layer until the solution pH value is 1, precipitating a large amount of white solid, stirring for 1 hour at 0 ℃, suction-filtering, leaching the solid with cooled 500mL ethyl acetate once, and drying at 60 ℃ to obtain 155g of N-methyltyramine hydrochloride product, wherein the yield is 88% and the purity is 99.0%.
Example 6
Condensation reaction: 153g of p-hydroxyphenylacetic acid is dissolved in 200mL of trichloromethane, 120g of thionyl chloride is dripped at 0 ℃, the mixture is refluxed and stirred for 5 hours until TLC detection reaction is finished, the mixture is dripped into 800mL of 40% methylamine water solution after cooling, the mixture is stirred for 2 hours under heat preservation after dripping, suction filtration is carried out, and filter cakes are leached by water to obtain 150g of yellow solid intermediate;
reduction reaction: 1000mL of toluene is added into a 10L reaction bottle, the intermediate is added, 78g of potassium borohydride is added at room temperature, 110g of zinc chloride is added in batches, and after the completion, reflux stirring is carried out overnight. After TLC detection reaction is finished, slowly pouring the reaction liquid into 2000mL of 6mol/L diluted hydrochloric acid, stirring for 1 hour, dropwise adding an aqueous sodium hydroxide solution until the pH value is 7, stirring for 1 hour, filtering, separating liquid, introducing hydrogen chloride gas into a toluene layer after drying until the solution pH value is 1, precipitating a large amount of white solid, stirring for 1 hour at 0 ℃, performing suction filtration, leaching the solid once with 500mL of cooled toluene, and drying at 60 ℃ to obtain 150g of N-methyltyramine hydrochloride product, wherein the yield is 85% and the purity is 99.1%.
Comparative example 1
Condensation reaction: 153g of p-hydroxyphenylacetic acid is dissolved in 200mL of dichloromethane, 120g of thionyl chloride is dripped at 0 ℃, reflux stirring is carried out for 5 hours until TLC detection reaction is finished, the mixture is dripped into 800mL of 40% methylamine water solution after cooling, heat preservation stirring is carried out for 2 hours after dripping is finished, suction filtration is carried out, and filter cakes are leached by water to obtain 150g of yellow solid intermediate;
reduction reaction: 1000mL of tetrahydrofuran was added to a 10L reaction flask, the intermediate was added, and 76g of sodium borohydride was added at room temperature and stirred under reflux overnight. After TLC detection reaction is finished, slowly pouring the reaction liquid into 2000mL of 6mol/L diluted hydrochloric acid, stirring for 1 hour, dropwise adding an aqueous sodium hydroxide solution until the pH value is 7, stirring for 1 hour, filtering, separating liquid, introducing hydrogen chloride gas into a dried tetrahydrofuran layer until the solution pH value is 1, precipitating a large amount of white solid, stirring for 1 hour at 0 ℃, suction filtering, leaching the solid with cooled 500mL ethyl acetate once, and drying at 60 ℃ to obtain 130g of N-methyltyramine hydrochloride product, wherein the yield is 74% and the purity is 98%.
Wherein the amount of substance is mass/molecular weight, and the ratio of the amounts of substance of p-hydroxyphenylacetic acid to thionyl chloride in example 1 is (153g/152.15 g/mol): (120g/118.97g/mol) ≈ 1.0055865:1.0086576 ≈ 1:1, and is calculated by such conversion in other examples.
Then, a sample of the N-methyltyramine hydrochloride synthesized by the method is extracted and detected by liquid chromatography.
Detection conditions are as follows: the instrument comprises the following steps: agilent 1100 hplc;
a chromatographic column: luna C18,4.6mm × 250mm,5 μm;
column temperature: 25 ℃;
flow rate: 1.0 ml/min;
detection wavelength: 210 nm;
sample introduction volume: 5.0 μ l;
mobile phase: acetonitrile: 0.1% phosphoric acid aqueous solution 60: 40 (v/v);
operating time: and (3) 30 min.
The liquid chromatogram of the detected sample is shown in FIG. 1; the analysis results are shown in table 1.
Table 1: the chromatographic analysis result of the N-methyl phenylethanolamine hydrochloride sample synthesized by the method
| Peak number | Peak area (μ V s) | Peak height (mu V) | Purity (%) |
| 1 | 1.2001 | 0.12 | 0.010 |
| 2 | 2.2117 | 0.24 | 0.018 |
| 3 | 3.2665 | 0.31 | 0.027 |
| 4 | 12170.9229 | 1160.02 | 99.945 |
| Total of | 12176.4011 | 1160.69 | 100 |
As can be seen from fig. 1 and table 1: the purity of the N-methyltyramine hydrochloride synthesized by the method is high and reaches 99.945%.
The specific embodiments described herein are merely illustrative of the spirit of the invention. Various modifications or additions may be made to the described embodiments or alternatives may be employed by those skilled in the art without departing from the spirit or ambit of the invention as defined in the appended claims.
While the invention has been described in detail and with reference to specific embodiments thereof, it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope thereof.
Claims (6)
1. The synthesis method of the N-methyltyramine hydrochloride is characterized by comprising the following steps:
condensation reaction: dissolving p-hydroxyphenylacetic acid in a first solvent, adding thionyl chloride, refluxing and stirring until the reaction is complete, cooling, dripping the reaction solution into a methylamine aqueous solution, keeping the temperature and stirring after dripping, and filtering to obtain an intermediate; the first solvent is one or more of dichloromethane, trichloromethane, tetrahydrofuran, acetone, butanone and toluene;
reduction reaction: dissolving the intermediate in a second solvent, firstly adding one or two of reducing agents sodium borohydride and potassium borohydride at room temperature, then adding Lewis acid in batches, heating, refluxing and stirring overnight, introducing the reaction liquid into an acid solution after the reaction is finished, then adjusting the pH value to be neutral, filtering and separating liquid after stirring, introducing hydrogen chloride gas into the second solvent layer until the hydrogen chloride gas is saturated and the pH value of the solution is 1, stirring, carrying out suction filtration, leaching the solid, and drying to obtain the N-methyl tyramine hydrochloride.
2. The method for synthesizing N-methyltyramine hydrochloride according to claim 1, wherein the mass ratio of p-hydroxyphenylacetic acid to thionyl chloride in the condensation reaction is 1:0.8 to 1.5.
3. The method of claim 1, wherein the temperature of thionyl chloride added during the condensation reaction is-5 to 5 ℃.
4. The method of claim 1, wherein the lewis acid used in the reduction reaction is one or more of aluminum trichloride, zinc chloride, lithium chloride, calcium chloride, and ferric chloride.
5. The method of synthesizing N-methyltyramine hydrochloride according to claim 1 or 4, wherein the mass ratio of the reducing agent to the Lewis acid in the reduction reaction is 1: 0.4-1.2.
6. The method for synthesizing N-methyltyramine hydrochloride according to claim 1, wherein the solvent II in the reduction reaction is one or more of methyl tert-butyl ether, toluene, ethyl acetate, tetrahydrofuran and ethylene glycol dimethyl ether.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710156217.5A CN106977411B (en) | 2017-03-16 | 2017-03-16 | Synthetic method of N-methyltyramine hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710156217.5A CN106977411B (en) | 2017-03-16 | 2017-03-16 | Synthetic method of N-methyltyramine hydrochloride |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106977411A CN106977411A (en) | 2017-07-25 |
| CN106977411B true CN106977411B (en) | 2020-01-03 |
Family
ID=59338259
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710156217.5A Expired - Fee Related CN106977411B (en) | 2017-03-16 | 2017-03-16 | Synthetic method of N-methyltyramine hydrochloride |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106977411B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114621101A (en) * | 2020-12-11 | 2022-06-14 | 李冰坚 | Refining method of 3, 5-dimethyl-1, 2-phenylenediamine dihydrochloride |
| CN113620821A (en) * | 2021-09-01 | 2021-11-09 | 广汉市派瑞林科技有限责任公司 | Preparation method of hordenine hydrochloride |
| CN113683522A (en) * | 2021-09-01 | 2021-11-23 | 广汉市派瑞林科技有限责任公司 | Preparation method of N-methyltyramine hydrochloride |
| CN114853619B (en) * | 2022-05-19 | 2024-05-10 | 神隆医药（常熟）有限公司 | Preparation method of N-methyltyramine hydrochloride suitable for industrial production |
-
2017
- 2017-03-16 CN CN201710156217.5A patent/CN106977411B/en not_active Expired - Fee Related
Non-Patent Citations (3)
| Title |
|---|
| Process Development and Pilot-Scale Synthesis of New Cyclization Conditions of Substituted Phenylacetamides to Tetrahydroisoquinoline-2-ones Using Eaton"s Reagent;Luckner G. Ulysse et al.;《Organic Process Research & Development》;20091117;第14卷;第225-228页 * |
| Total synthesis and biological evaluation of methylgerambullone;Jong Taik Moon et al.;《Bioorganic & Medicinal Chemistry Letters》;20091114;第20卷;第52-55页 * |
| 酰胺还原反应研究进展;陈晓 等;《化学通报》;20011231(第12期);第749-754页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106977411A (en) | 2017-07-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106977411B (en) | Synthetic method of N-methyltyramine hydrochloride | |
| CN105218621B (en) | Dehydroabietic acid benzimidazole Schiff base heterocyclic derivatives with anti-tumor activity and preparation method therefor and application thereof | |
| CN103360395B (en) | A kind of indole carbazole compound and its preparation method and application | |
| JP6558968B2 (en) | Oligomer containing epicatechin and method for producing the same | |
| CN105085458B (en) | A kind of synthetic method of coumarin derivatives | |
| Oizumi et al. | Synthesis of Procyanidins C2 and C1 Using Lewis Acid Mediated Equimolar Condensation | |
| CN113429300B (en) | Paraalkyl-7-base secondary amine compound, preparation method and weeding application thereof | |
| CN110511193A (en) | A kind of α -one thioamide analog compound and its synthetic method | |
| CN100478333C (en) | Chiral and non-chiral diimidazolinylbenzene compounds and synthesis method | |
| CN115322100A (en) | Delta, epsilon-alkenyl ketone compound and preparation method and application thereof | |
| CN111253392B (en) | Method for preparing apixaban | |
| CN101327450A (en) | Aminoacid ion liquid carried Salen metallic catalyst and preparation method | |
| JP2014114283A (en) | Method for producing polyphenol | |
| KR20190022533A (en) | METHOD OF PRODUCING IRON COMPLEX AND METHOD OF PRODUCING ESTER COMPOUND USING IRON COMPLEX | |
| CN102070587B (en) | One kettle way prepares the method for Simvastatin | |
| CN108404979B (en) | Thiourea-proline chiral catalyst and synthesis method and application thereof | |
| CN103641937A (en) | New green synthesis technology of ethylated-beta-cyclodextrin | |
| CN105622642A (en) | Voriconazole copper nitrate complex with bacteriostatic activity and preparation method thereof | |
| CN104478803A (en) | Preparation method of varenicline intermediate and nitroreduction impurity thereof | |
| CN103570618A (en) | Preparation method of montelukast sodium | |
| CN112500324B (en) | Method for preparing thioamide compound | |
| CN108383813B (en) | Penicic acid crystal form I and preparation method and application thereof | |
| CN103214359B (en) | Method for preparing curcumin oligomer | |
| JP5291335B2 (en) | Tricine production method | |
| CN108558818B (en) | Preparation method of methoxymethyl alkenyl compound |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20210125 Address after: No. 36, Meihua Avenue, Xuyi Economic Development Zone, Huai'an City, Jiangsu Province Patentee after: Xuyi Lingkai Pharmaceutical Technology Co.,Ltd. Address before: 215200 Room 301, C9 / F, bio nano Park, 218 Xinghu street, Suzhou Industrial Park, Suzhou City, Jiangsu Province Patentee before: SUZHOU UUGENE BIOPHARMA Co.,Ltd. |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20200103 |