CN116947644A - Preparation method of memantine hydrochloride - Google Patents
Preparation method of memantine hydrochloride Download PDFInfo
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- CN116947644A CN116947644A CN202310925615.4A CN202310925615A CN116947644A CN 116947644 A CN116947644 A CN 116947644A CN 202310925615 A CN202310925615 A CN 202310925615A CN 116947644 A CN116947644 A CN 116947644A
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- memantine hydrochloride
- reaction
- dimethyl adamantane
- preparation
- anhydrous
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- LDDHMLJTFXJGPI-UHFFFAOYSA-N memantine hydrochloride Chemical compound Cl.C1C(C2)CC3(C)CC1(C)CC2(N)C3 LDDHMLJTFXJGPI-UHFFFAOYSA-N 0.000 title claims abstract description 43
- 229960000967 memantine hydrochloride Drugs 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 42
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 36
- 238000006243 chemical reaction Methods 0.000 claims abstract description 31
- 238000000034 method Methods 0.000 claims abstract description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 26
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 claims abstract description 24
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000000706 filtrate Substances 0.000 claims abstract description 17
- 230000008569 process Effects 0.000 claims abstract description 14
- RTPQXHZLCUUIJP-UHFFFAOYSA-N 1,2-dimethyladamantane Chemical class C1C(C2)CC3CC1C(C)C2(C)C3 RTPQXHZLCUUIJP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000004519 manufacturing process Methods 0.000 claims abstract description 12
- 229910001923 silver oxide Inorganic materials 0.000 claims abstract description 12
- QUCXLVDIVQWYJR-UHFFFAOYSA-N 1-bromo-3,5-dimethyladamantane Chemical compound C1C(C2)CC3(C)CC1(C)CC2(Br)C3 QUCXLVDIVQWYJR-UHFFFAOYSA-N 0.000 claims description 6
- PXDRFQZLDWZHPX-UHFFFAOYSA-N 1-chloro-3,5-dimethyladamantane Chemical group C1C(C2)CC3(C)CC1(C)CC2(Cl)C3 PXDRFQZLDWZHPX-UHFFFAOYSA-N 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 239000012065 filter cake Substances 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000000967 suction filtration Methods 0.000 abstract description 13
- 239000003054 catalyst Substances 0.000 abstract description 9
- 239000002253 acid Substances 0.000 abstract description 6
- 239000011230 binding agent Substances 0.000 abstract description 6
- 239000007810 chemical reaction solvent Substances 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 231100000252 nontoxic Toxicity 0.000 abstract description 2
- 230000003000 nontoxic effect Effects 0.000 abstract description 2
- 239000002904 solvent Substances 0.000 abstract description 2
- 229960003805 amantadine Drugs 0.000 abstract 1
- -1 amantadine compound Chemical class 0.000 abstract 1
- 229910021529 ammonia Inorganic materials 0.000 abstract 1
- 229910052799 carbon Inorganic materials 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 239000000047 product Substances 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 7
- 238000012216 screening Methods 0.000 description 7
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000004202 carbamide Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 238000006396 nitration reaction Methods 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 230000004075 alteration Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 229940099433 NMDA receptor antagonist Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229960004640 memantine Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000002341 toxic gas Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/04—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups
- C07C209/06—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms
- C07C209/08—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms with formation of amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
- B01J23/48—Silver or gold
- B01J23/50—Silver
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
- C07C2603/74—Adamantanes
Abstract
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of memantine hydrochloride. The invention takes halogenated dimethyl adamantane as an initial raw material, takes anhydrous N, N-dimethylformamide as a reaction solvent, adds active catalyst silver oxide and acid-binding agent triethylamine, introduces ammonia gas at the temperature of 80-85 ℃ under the pressure of 0.5MPa for reaction for 5-6 hours, and then reacts filtrate with concentrated hydrochloric acid after suction filtration to obtain memantine hydrochloride. The solvent anhydrous N, N-dimethylformamide used in the preparation method of the memantine hydrochloride is nontoxic, ammonia is directly introduced under a certain pressure in the presence of an active catalyst, and carbon-nitrogen bonds are directly formed by carbon halogen bonds to obtain the amantadine compound, so that the process for preparing the memantine hydrochloride is greatly simplified, the process route is short, the operation is easy, the production cost is low, the yield and the purity are high, and the method is suitable for large-scale industrial production.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of memantine hydrochloride.
Background
Memantine hydrochloride (memantine hydrochloride), also known as 1-amino-3, 5-dimethyladamantane hydrochloride, memantine hydrochloride, is a low-medium affinity, voltage-dependent and non-competitive NMDA receptor antagonist developed by Merz, germany, which can prevent apoptosis and improve memory, and is a new generation of drugs for improving cognitive functions. Thus, memantine hydrochloride has great potential for economic and social benefits.
Common synthetic methods of memantine hydrochloride mainly include urea method (CN 1594277A), acetonitrile method (CN 102432473A), and formamide method (Huber F A, gallo G, faveri C D.process for the manufacture of memantine and inrermediate product: WO, 2009115334A2[P)]2009-09-24.), nitration (Huang Bin, ao Guizhen, improvement of the synthesis process of memantine hydrochloride [ J]Chinese pharmaceutical industry, 2009, 18 (22): 17-18.), but the reaction difficulty of the urea method 1-bromo-3, 5-dimethyl adamantane and urea is high, the reaction yield is lower than 70%, and the industrial production cost is high; concentrated sulfuric acid and organic acid are used for reaction in the acetonitrile method, the reaction is severe, the toxicity is high, and the yield is low; the formamide method can generate a large amount of reddish brown toxic gas NO in the reaction process 2 Post-treatment is complex; in the process of the nitration method, pd/C catalytic hydrogenation is needed, so that the nitration method has high danger, long time and high cost. The existing synthesis methods have the problems of high production cost, large harm to human bodies, low yield and the like at different degrees.
Disclosure of Invention
Aiming at the problems, the invention provides the preparation method of the memantine hydrochloride, which has the advantages of raw materials of commercial general chemicals, high yield, low synthesis cost, application of active catalyst catalysis, short reaction route and time and small harm to human bodies.
The technical scheme of the invention is as follows:
the preparation method of memantine hydrochloride comprises the following specific steps:
(1) Dissolving halogenated dimethyl adamantane in anhydrous N, N-dimethylformamide, adding silver oxide and triethylamine, heating, introducing ammonia gas for ammoniation, cooling to room temperature after the reaction is finished, and suction filtering to obtain filtrate;
(2) And cooling the filtrate to room temperature, adding concentrated hydrochloric acid, stirring at room temperature, filtering, and drying the filter cake to obtain memantine hydrochloride.
The reaction equation is shown in formula I:
preferably, in the step (1), the temperature is 80-85 ℃ and the pressure is 0.5MPa when ammonia gas is introduced.
Preferably, in step (1), the reaction time is from 5 to 6 hours.
Preferably, in the step (1), the halogenated dimethyl adamantane is calculated according to the mass ratio: anhydrous N, N-dimethylformamide = 1:4.5 to 5.5.
Preferably, in the step (1), the halogenated dimethyl adamantane is calculated according to the molar ratio: triethylamine = 1:1.0 to 1.1.
Preferably, in the step (1), the halogenated dimethyl adamantane is calculated according to the mass ratio: silver oxide = 1:0.01 to 0.05.
Preferably, in step (1), the halogenated dimethyladamantane is 1-chloro-3, 5-dimethyladamantane or 1-bromo-3, 5-dimethyladamantane.
Preferably, in the step (2), the halogenated dimethyl adamantane is calculated according to the mass ratio: concentrated hydrochloric acid=1: 5 to 6; the concentration of the concentrated hydrochloric acid is 35-38%.
Preferably, in the step (2), the stirring time is 1h.
The beneficial effects of the invention are as follows:
(1) The invention provides a new method for preparing memantine hydrochloride, which avoids using reagents such as acetonitrile, diethyl ether and the like which have great harm to the environment and human bodies in a synthetic route, and the solvent used in the method is basically nontoxic, the raw materials are common, the toxicity is low, the price is low, and the production cost is low;
(2) The method has the advantages of short synthetic route, simple and easy operation by using the active catalyst, no need of purification, reduced operation steps, high product stability, no high pollution gas and byproducts in the production process, relative safety and environmental protection, and suitability for large-scale industrial production;
(3) The reaction temperature and pressure and the used reagent are increased when ammonia gas is introduced through a sieving gate, so that the purity and the yield of the product are improved; the reaction temperature is higher than 85 ℃, byproducts are increased, the temperature is lower than 80 ℃, and the reaction time can be prolonged; impurities are easy to generate when the pressure is higher than 0.5MPa, and the reaction is slow or non-reaction when the pressure is lower than 0.5 MPa; the final product yield and purity using other reagents are not as good as those used in the present process. The total yield of the final product prepared by the method can reach more than 80 percent, and the purity can reach more than 98 percent.
Detailed Description
The present invention is further described in detail below with reference to examples, wherein the concentration of concentrated hydrochloric acid used in the examples is 36%, and the details are not described in detail below.
Example 1
Anhydrous N, N-dimethylformamide (995.5 g) and 1-chloro-3, 5-dimethyl adamantane (199 g) are added into an autoclave, silver oxide (2.13 g) and triethylamine (101.8 g) are added in a dark place, then the temperature is raised to 80 ℃, the pressure is controlled to be 0.5MPa, ammonia gas is introduced for reaction for 5.5 hours, after the reaction is finished, the ammonia gas is stopped, the temperature is reduced, and the filtrate is obtained through suction filtration; after the filtrate is cooled, concentrated hydrochloric acid (1000 g) is added, the mixture is stirred for 1h at room temperature, and then suction filtration is carried out, and a filter cake is dried to obtain 178g of memantine hydrochloride, wherein the yield is 82.4%, and the purity is 98.2%. The color state of the obtained product: white powder, melting point: 292 ℃. 1 H-NMR(CDC1 3 )：0.85(s，6H)，1.15(m，2H)，1.26(q，J＝12.5Hz，4H)，1.65(d，J＝11.5Hz，4H)，1.85(s，2H)，8.27(s，3H)。
Example 2
Anhydrous N, N-dimethylformamide (899.6 g) and 1-chloro-3, 5-dimethyl adamantane (199 g) are added into an autoclave, silver oxide (5.97 g) and triethylamine (110.9 g) are added in a dark place, then the temperature is raised to 85 ℃, the pressure is controlled to be 0.5MPa, ammonia gas is introduced for reaction for 5 hours, after the reaction is finished, the ammonia gas is stopped, the temperature is reduced, and the filtrate is obtained through suction filtration; after the filtrate was cooled, concentrated hydrochloric acid (1095 g) was added thereto, stirred at room temperature for 1 hour, and then suction filtration was performed, and the cake was dried to obtain 181g memantine hydrochloride, yield 83.9%, purity 98.4%.
Example 3
Anhydrous N, N-dimethylformamide (1091.2 g) and 1-chloro-3, 5-dimethyl adamantane (199 g) are added into an autoclave, silver oxide (9.91 g) and triethylamine (105.6 g) are added in a dark place, then the temperature is raised to 83 ℃, the pressure is controlled to be 0.5MPa, ammonia gas is introduced for reaction for 6 hours, after the reaction is finished, the ammonia gas is stopped, the temperature is reduced, and the filtrate is obtained through suction filtration; after the filtrate was cooled, concentrated hydrochloric acid (1191 g) was added, stirred at room temperature for 1 hour, and suction filtration was performed, and the cake was dried to obtain 183g memantine hydrochloride, yield 84.8%, purity 98.5%.
Example 4
Anhydrous N, N-dimethylformamide (1095.4 g) and 1-bromo-3, 5-dimethyl adamantane (243 g) are added into an autoclave, silver oxide (3.25 g) and triethylamine (102.2 g) are added in a dark place, then the temperature is raised to 80 ℃, the pressure is controlled to be 0.5MPa, ammonia gas is introduced for reaction for 5 hours, after the reaction is finished, the ammonia gas is stopped, the temperature is reduced, and the filtrate is obtained through suction filtration; after the filtrate was cooled, concentrated hydrochloric acid (1220 g) was added, stirred at room temperature for 1 hour, and suction filtration was performed, and the cake was dried to obtain 180g of memantine hydrochloride, yield 83.4%, purity 98.4%.
Example 5
Anhydrous N, N-dimethylformamide (1331.2 g) and 1-bromo-3, 5-dimethyl adamantane (243 g) are added into an autoclave, silver oxide (11.92 g) and triethylamine (110.5 g) are added in a dark place, then the temperature is raised to 85 ℃, the pressure is controlled to be 0.5MPa, ammonia gas is introduced for reaction for 6 hours, after the reaction is finished, the ammonia gas is stopped, the temperature is reduced, and the filtrate is obtained through suction filtration; after the filtrate was cooled, concentrated hydrochloric acid (1450 g) was added, stirred at room temperature for 1 hour, and suction filtration was performed, and the cake was dried to obtain 177g of memantine hydrochloride, with a yield of 82.1% and a purity of 98.3%.
Example 6
Anhydrous N, N-dimethylformamide (1215.5 g) and 1-bromo-3, 5-dimethyl adamantane (243 g) are added into an autoclave, silver oxide (8.55 g) and triethylamine (105.9 g) are added in a dark place, then the temperature is raised to 82 ℃, the pressure is controlled to be 0.5MPa, ammonia gas is introduced, the reaction is carried out for 5.5 hours, after the reaction is finished, the ammonia gas is stopped, the temperature is reduced, and the filtrate is obtained through suction filtration; after the filtrate was cooled, concentrated hydrochloric acid (1337 g) was added, stirred at room temperature for 1 hour, and suction filtration was performed, and the cake was dried to obtain 175g of memantine hydrochloride, with a yield of 81.1% and a purity of 98.1%.
Comparative example 1 temperature and pressure screening
1.1 temperature screening
This comparative example provides a process for the preparation of memantine hydrochloride, which differs from example 1 in that: the reaction temperature was changed separately in example 1, and the product yield and purity were as in example 1, as shown in Table 1.
TABLE 1 purity of product yield
In the whole experimental process, the reaction time can be prolonged when the temperature is lower than 80 ℃, and the yield is reduced; a temperature higher than 85 ℃ will increase byproducts, affecting purity; therefore, the optimal reaction temperature of memantine hydrochloride is 80-85 ℃.
1.2 pressure screening
This comparative example provides a process for the preparation of memantine hydrochloride, which differs from example 1 in that: the reaction pressure was changed in example 1 alone, and the product yield and purity were as in example 1 and are shown in Table 2.
TABLE 2 purity of product yield
In the whole experimental process, the pressure is lower than 0.5MPa, the reaction time can be prolonged, and even the reaction is not performed; the temperature is higher than 0.5MPa, which can increase byproducts and affect the purity of the product; therefore, the reaction pressure of memantine hydrochloride should be controlled at 0.5MPa. Comparative example 2 screening of catalyst, acid-binding agent, reaction solvent
2.1 screening of catalysts
This comparative example provides a process for the preparation of memantine hydrochloride, which differs from example 1 in that: the catalyst type was changed in example 1 alone, and the product yield and purity were as in example 1 and are shown in Table 3.
TABLE 3 purity of product yield
2.2 screening of acid binding Agents
This comparative example provides a process for the preparation of memantine hydrochloride, which differs from example 1 in that: the species of the acid-binding agent in example 1 was changed separately, and the product yield and purity were as in example 1 and are shown in Table 4.
TABLE 4 purity of product yield
2.3 screening of reaction solvents
This comparative example provides a process for the preparation of memantine hydrochloride, which differs from example 1 in that: the reaction solvent anhydrous N, N-dimethylformamide in example 1 was replaced with dimethyl sulfoxide, and the final product was obtained in 76.2% yield and 97.3% purity in the same manner as in example 1.
In conclusion, the change of the catalyst, the acid binding agent and the reaction solvent can reduce the yield of the product to a certain extent, generate impurities and influence the purity of the product. Therefore, the invention selects silver oxide as a catalyst, triethylamine as an acid binding agent and anhydrous N, N-dimethylformamide as a reaction solvent to prepare the memantine hydrochloride.
The foregoing are all preferred embodiments of the present invention, but it should not be construed that the scope of the above-described subject matter of the present invention is limited to only the above-described embodiments. Various substitutions and alterations are made according to the ordinary skill and familiar means of the art without departing from the technical spirit of the invention, and all such substitutions and alterations are intended to be included in the scope of the invention.
Claims (9)
1. The preparation method of memantine hydrochloride is characterized by comprising the following specific steps:
(1) Dissolving halogenated dimethyl adamantane in anhydrous N, N-dimethylformamide, adding silver oxide and triethylamine, heating, introducing ammonia gas, starting to react, cooling after the reaction is finished, and filtering to obtain filtrate;
(2) And cooling the filtrate, adding concentrated hydrochloric acid, stirring at room temperature, filtering, and drying the filter cake to obtain memantine hydrochloride.
2. The process for producing memantine hydrochloride according to claim 1, wherein in the step (1), the temperature is 80 to 85 ℃ and the pressure is 0.5MPa when ammonia gas is introduced.
3. The process for preparing memantine hydrochloride according to claim 1, wherein in step (1), the reaction time is 5 to 6 hours.
4. The method for producing memantine hydrochloride according to claim 1, wherein in the step (1), halogenated dimethyl adamantane is obtained by mass ratio: anhydrous N, N-dimethylformamide = 1:4.5 to 5.5.
5. The process for the preparation of memantine hydrochloride according to claim 1, characterized in that in step (1), in terms of molar ratio, the halogenated dimethyl adamantane: triethylamine = 1:1.0 to 1.1.
6. The method for producing memantine hydrochloride according to claim 1, wherein in the step (1), halogenated dimethyl adamantane is obtained by mass ratio: silver oxide = 1:0.01 to 0.05.
7. The method for producing memantine hydrochloride according to claim 1, wherein in step (1), the halogenated dimethyl adamantane is 1-chloro-3, 5-dimethyl adamantane or 1-bromo-3, 5-dimethyl adamantane.
8. The method for producing memantine hydrochloride according to claim 1, wherein in the step (2), halogenated dimethyl adamantane is obtained by mass ratio: concentrated hydrochloric acid=1: 5 to 6.
9. The method for producing memantine hydrochloride according to claim 1, wherein in said step (2), the stirring time is 1h.
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