CN113493388B

CN113493388B - Synthesis method of butenafine hydrochloride

Info

Publication number: CN113493388B
Application number: CN202010268275.9A
Authority: CN
Inventors: 于成彬; 张乃华
Original assignee: Lunan Pharmaceutical Group Corp
Current assignee: Lunan Pharmaceutical Group Corp
Priority date: 2020-04-08
Filing date: 2020-04-08
Publication date: 2024-05-10
Anticipated expiration: 2040-04-08
Also published as: CN113493388A

Abstract

The invention belongs to the technical field of medicine synthesis, and particularly relates to a method for synthesizing butenafine hydrochloride; n-methyl-1-naphthylmethylamine and p-tert-butyl benzyl alcohol are used as raw materials to synthesize the butenafine under the action of a catalyst. Salifying by using HCl/organic solvent, filtering, and drying the filter cake under reduced pressure to obtain butenafine hydrochloride; the product obtained by the invention has higher purity and yield.

Description

Synthesis method of butenafine hydrochloride

Technical Field

The invention belongs to the technical field of medicine synthesis, and particularly relates to a method for synthesizing butenafine hydrochloride.

Background

Butenafine hydrochloride (butenafine hydrochloride), chemical name N- (4-tert-butylphenyl) -N-methyl-1-naphthamine hydrochloride, is an allylamine antifungal agent developed by Japanese scientific Co., ltd, and was first marketed in Japan in 1992 under the trade name Mentax. The product can inhibit the activity of fungus squalene cyclooxygenase with high selectivity, and inhibit the biosynthesis of squalene and ergosterol in fungus body, thereby destroying the generation of fungus cell membrane and leading to fungus death. Has the characteristics of broad antibacterial spectrum, high antibacterial activity, low recurrence rate, small side effect and the like, and is widely applied to clinic. The chemical structure is as follows:

The currently reported synthetic processes for butenafine mainly include the following:

The main process is reported in patent EP221781, CN1597660A, CN1727325A, CN101077858A, yakugaku Zasshi,1991,111 (2): 126-137, journal of Chinese medical industry, 1999, (3): 102-103, etc. Naphthalene (or its downstream intermediate) is used as raw material, firstly chloromethylated to synthesize 1-chloromethylnaphthalene, then reacted with methylamine to produce N-methylnaphthalene methylamine, then reacted with p-tert-butyl benzyl halide to produce butenafine hydrochloride by substitution, salification and other reactions. The route is as follows:

The route has the advantages of readily available raw materials, simple operation and the like. However, the reaction is usually carried out in dry DMF with anhydrous sodium carbonate or anhydrous potassium carbonate as acid-binding agent. DMF has a high boiling point and is inconvenient to recycle; the p-tert-butyl bromobenzyl is usually obtained from p-methyl-tert-Ding Benxiu generation, and the preparation method has the advantages of more byproducts, larger pollution and higher cost, and is not suitable for industrial workshop production because of the strict operations such as reduced pressure distillation and the like for refining the p-tert-butyl bromobenzyl. Meanwhile, due to the fact that the side-chain halohydrocarbon is used in the N-alkylation reaction in excess and the reaction temperature is high, disubstituted impurities are easy to generate, quaternary ammonium salt structural intermediates are further generated, quaternary ammonium salt impurities are easy to generate in the synthesis of finished products, the purity of the products is low, and the total yield is low after further refining (related structures of the impurities are shown as follows).

German application chemistry Angew.chem.int.ed.,2014,53 (41), 11010-11014 reports the preparation of the target product under ruthenium catalysis starting from 1-naphthaldehyde and 4-tert-butylbenzylamine with carbon dioxide as carbon source. The route is as follows:

However, the whole process in this method is complicated to operate and is accompanied by the formation of a large amount of inorganic salt by-products. Moreover, the conversion of the end product described above needs to be carried out at very high pressures [ CO ₂/H₂ (20/60 bar) ] and requires high equipment operating requirements. In addition, the noble metal ruthenium is used for catalysis, so that the ruthenium catalyst is high in price, and the production cost is high.

Org.chem.,2018,83,11886-11895, under the catalysis of cadmium selenide/cadmium sulfide and visible light, reduced with 4-fluorobenzene thiol, followed by diisopropyl azodicarboxylate (DIAD) and triphenylphosphine. Reacting with methyl iodide in the presence of the catalyst to obtain the target product. The route is as follows:

However, the process uses heavy metal cadmium compounds with high toxicity to synthesize key intermediates, and the limit requirement is extremely low; when the target product is prepared, methyl is introduced by taking methyl iodide with higher toxicity and lower boiling point as a carbon source, N-polyalkylated quaternary ammonium salt impurities are also introduced, and in addition, the generated triphenylphosphine oxide after the reaction has lower yield after repeated refining due to poor solubility.

In addition, in recent years, quality control of crude drugs has been increasingly focused on research on genotoxic (or genotoxic) impurities. The genetic material of human body is damaged when the concentration of the genotoxic impurities is very low, so that the genetic mutation is caused and the occurrence of tumors can be promoted. Therefore, the method has important practical significance in strictly controlling the content of related genotoxic impurities in the production process. In the process, the reactant monohalogenated alkane and naphthaldehyde have genotoxicity warning structures, and risk assessment and strict requirements are required for the reactant monohalogenated alkane and naphthaldehyde.

Patent US5021458 uses 1-naphthoic acid as raw material, and uses thionyl chloride to make chlorination to obtain 1-naphthoyl chloride, then uses the 1- (4-tert-butyl benzene) -N-methyl methylamine to make condensation reaction to obtain N- (4-tert-butyl benzyl) -N-methyl-1-naphthoyl amide, and finally uses lithium aluminium hydride to make reduction and salification so as to obtain the invented butenafine hydrochloride. The route is as follows:

In addition, the patent reports a method for preparing butenafine hydrochloride by using p-tert-butylbenzoic acid as a raw material, chloridizing the p-tert-butylbenzoyl chloride by using thionyl chloride, condensing the p-tert-butylbenzoyl chloride with N-methylnaphthylamine to obtain 4-tert-butyl-N-methyl-N- (methylnaphthylamine) benzamide, and reducing the 4-tert-butyl-N-methyl-N- (methylnaphthylamine) benzamide by using lithium aluminum hydride to form salt. The route is as follows:

However, the two methods need to use acyl chloride with high toxicity and irritation, and have high equipment requirements and need to be carried out in a special reaction room; meanwhile, lithium aluminum hydride with high activity is needed for the reduction reaction, so that the operation risk is high, and meanwhile, the production cost is high, so that the method is not suitable for large-scale preparation.

Patent CN105130823B discloses a method for obtaining butenafine by taking 4-tert-butylbenzylamine as raw material, reacting with 1-naphthoyl chloride and formic acid in organic solvent, taking organosilane compound [ diphenylsilane, diethylsilane, poly (methylhydrosiloxane), phenylsilane ] as reducing agent, and taking nonmetallic boron compound [ triethylboron, tris (pentafluorophenylboron) ] as catalyst to perform N-methylation reaction, and reducing amide bond. The route is as follows:

the literature angel.chem.int.ed. 2015,54,9042-9046 uses 1-naphthoic acid as raw material, and uses formic acid as carbon source to prepare butenafine after phenylboronic acid catalysis and reduction by organosilane compound and nonmetallic boron compound. The route is as follows:

however, the method is applied to organosilane compounds and nonmetallic boron compounds with higher price when carrying out reduction reaction, so that the production cost is higher, and meanwhile, the reaction temperature of the latter is higher, the reaction time is longer, and the method is not suitable for industrial production.

In summary, in the technical processes for preparing butenafine that have been reported, there are mainly the following problems:

(1) The haloalkane is used for N-alkylation reaction, N-peralkylation impurities are easy to generate, and further refining is needed;

(2) The reduction and ammonification process needs to use ruthenium with high price as a catalyst, so that the production cost is high;

(3) The N-alkylation reaction material monohalogenated alkane and naphthaldehyde have a genotoxicity warning structure, and risk assessment and strict requirements are required for the N-alkylation reaction material monohalogenated alkane and naphthaldehyde;

(4) The N-alkyl side chain is introduced through amide reduction, but the method needs to be applied to lithium aluminum hydride or an organosilane compound/nonmetal boron compound as a reducing agent, so that the reaction conditions are more severe, and the production cost is higher;

(5) Heavy metal cadmium compounds with high toxicity are required to be applied in the reductive amination process, so that the detection limit of the finished product is extremely low.

In view of the problems of the prior art, the research and search of a preparation method which has the advantages of mild reaction conditions, simple operation process, high product yield, high purity and low production cost and is suitable for industrial production of the butenafine still needs to be solved at present.

Disclosure of Invention

Aiming at the problems of the existing preparation technology of butenafine, the invention provides a synthesis method of butenafine hydrochloride. The method can effectively avoid N-peralkylation impurities and related genotoxicity warning structure impurities, and the prepared target product has higher purity and yield.

The specific technical scheme of the invention is as follows:

The synthesis method of butenafine hydrochloride comprises the steps of reacting N-methyl-1-naphthylamine with p-tert-butyl benzyl alcohol to obtain butenafine hydrochloride, wherein the reaction formula is as follows:

The synthesis method of the butenafine hydrochloride specifically comprises the following steps:

Under the protection of inert gas, adding a catalyst, N-methyl-1-naphthylmethylamine, p-tert-butyl benzyl alcohol and a reaction solvent into a sealing device, sealing and controlling the temperature until the reaction is finished, extracting by an extracting agent, concentrating an extract under reduced pressure, forming hydrochloride by an HCl/organic solvent, filtering, and drying a filter cake under reduced pressure to obtain the butenafine hydrochloride.

The catalyst is as follows: cp Ir complex catalyst and base combination system; wherein Cp Ir complex is preferably one of [ Cp IrI ₂]₂、[Cp*IrCl₂]₂; of these, a combination system of [ Cp ] IrCl ₂]₂ with a base is particularly preferred.

Preferably, the base is one of NaHCO ₃,Na₂CO₃,K₂CO₃, acONa, TEA or a combination thereof, with NaHCO ₃ being particularly preferred. The alkali can be prepared into aqueous solution of alkali or can be directly added into the reaction.

In another preferred embodiment the catalyst is an Rh based complex catalyst; preferably RhCl (one of PPh ₃)₃,RhH(PPh₃)₄;

preferably, the feeding mole ratio of the N-methyl-1-naphthylmethylamine to the p-tert-butyl benzyl alcohol is 1:1.0 to 1.1.

Preferably, the molar ratio of the N-methyl-1-naphthylmethylamine, the Cp-Ir complex catalyst and the base is 1:0.5% -5%: 1 to 10 percent. Of these, 1:2%:5%.

Preferably, the feeding mole ratio of the N-methyl-1-naphthylmethylamine to the Rh complex catalyst is 1:0.5% to 5%, of which 1:2%.

Preferably, the reaction solvent is one or a combination of deionized water, benzene, toluene, xylene, 1, 4-dioxane, acetonitrile, and deionized water is particularly preferred.

Preferably, the sealing device is placed in heating equipment with the temperature of 100-150 ℃ in the temperature control reaction. The heating device can be selected from heating equipment such as oil bath heating, electric heating sleeves, steam heating, electric furnaces and the like. The sealing equipment can be sealing glass tubes, stainless steel reaction kettles with good sealing performance, sealing Schlenk devices and the like. The present invention is preferably validated by Schlenk apparatus.

Preferably, the temperature-controlled reaction time is 5 to 10 hours; detection determinations may also be made.

Preferably, the extraction solvent is one or a combination of dichloromethane, chloroform and ethyl acetate.

Preferably, the HCl/organic solvent is one or a combination of HCl/methanol, HCl/ethanol, HCl/isopropanol, HCl/1, 4-dioxane, HCl/ethyl acetate, with HCl/methanol being particularly preferred;

preferably, the concentration of hydrochloric acid in the HCl/organic solvent is 0.5 to 4mol/L, of which 2mol/L is particularly preferred.

In the present invention, the inert gas is usually nitrogen or argon, and among them, argon is particularly preferable.

Compared with the prior art, the invention has the technical effects that:

(1) The catalyst of the invention enables N-alkylation monosubstituted reaction of p-tert-butyl benzyl alcohol and N-methyl-1-naphthylmethylamine to be carried out, effectively avoids N-peralkylation impurities, has small catalyst dosage, greatly reduces production cost, and improves the yield and purity of the obtained product.

(2) The crude product is refined through one-step salification, and meanwhile, the target product is obtained, the reaction steps are few, the post-treatment is simple, and the method is more suitable for industrial production.

Detailed Description

The invention is further illustrated by the following examples, with the understanding that: the examples of the present invention are intended to be illustrative of the invention and not to be limiting of the invention, so that simple modifications to the invention which are based on the method of the invention are within the scope of the invention as claimed.

The materials used in the experiment: the compound N-methyl-1-naphthylmethylamine is commercially available and can also be prepared by reference to the techniques disclosed in the prior art; the compound p-tert-butyl benzyl alcohol is commercially available and can also be prepared by reference to the techniques disclosed in the prior art; the materials used in the other experiments were not of the indicated source and specification, either commercially available analytically pure or chemically pure.

The invention adopts HPLC to measure the purity of the butenafine, and the chromatographic conditions are as follows:

Chromatographic column: welch Ultimate XB-C ₁₈ (4.6mm. Times.150mm, 3.0 μm);

mobile phase: acetate buffer (18.0 g of sodium acetate, 9.8mL of glacial acetic acid, diluted to 1000mL with water) -methanol-isopropanol (17:70:13);

column temperature: 30 ℃;

detection wavelength: 282nm;

flow rate: 1.0mL/min;

Sample injection amount: 10 mu L.

In the following examples, various processes and methods, which are not described in detail, are conventional methods well known in the art.

Example 1

Under the protection of argon, adding [ Cp ] IrCl ₂]₂ (1.59 g, 0.002mol), sodium bicarbonate (0.42 g,0.005 mol), N-methyl-1-naphthylmethylamine (17.12 g,0.10 mol), p-tert-butyl benzyl alcohol (16.42 g,0.10 mol) and deionized water (150 mL) into a Schlenk device, sealing and placing into an oil bath with a temperature of 110 ℃ until the reaction is completed for 8 hours, cooling the reaction liquid to room temperature, adding dichloromethane (50 mL multiplied by 3) for extraction, merging the extract liquid and concentrating under reduced pressure until the extract liquid is dry, adding HCl/methanol (150 mL,2 mol/L) for salifying, continuously stirring and crystallizing for 2-3 hours, filtering, decompressing and drying a filter cake to obtain butenafine hydrochloride, wherein the yield is 96.3 percent: 99.89%.

Example 2

Under the protection of nitrogen, adding [ Cp ] IrCl ₂]₂ (1.59 g, 0.002mol), sodium bicarbonate (0.42 g,0.005 mol), N-methyl-1-naphthylmethylamine (17.12 g,0.10 mol), p-tert-butyl benzyl alcohol (18.07 g,0.11 mol) and deionized water (150 mL) into a Schlenk device, sealing and placing the device into an oil bath with the temperature of 110 ℃ for reaction for 8 hours, cooling the reaction liquid to room temperature after the reaction is finished, adding dichloromethane (50 mL multiplied by 3) for extraction, merging the extract liquid, concentrating the extract liquid to dryness under reduced pressure, adding HCl/methanol (300 mL,0.5 mol/L) for salifying, continuously stirring and crystallizing for 2-3 hours, filtering, decompressing and drying a filter cake to obtain the butenafine hydrochloride with the yield of 96.8 percent, and performing HPLC:99.80%.

Example 3

Under the protection of argon, adding [ Cp ] IrCl ₂]₂ (1.59 g, 0.002mol), sodium bicarbonate (0.42 g,0.005 mol), N-methyl-1-naphthylmethylamine (17.12 g,0.10 mol), p-tert-butyl benzyl alcohol (18.89 g,0.115 mol) and deionized water (150 mL) into a Schlenk device, sealing and placing the device into an oil bath with the temperature of 110 ℃ for reaction for 8 hours, cooling the reaction liquid to room temperature after the reaction is finished, adding dichloromethane (50 mL multiplied by 3) for extraction, merging the extract liquid and concentrating the extract liquid to dryness under reduced pressure, adding HCl/1, 4-dioxane (150 mL,2 mol/L) for salifying, continuously stirring and crystallizing for 2-3 hours, filtering, decompressing and drying the filter cake to obtain the butenafine hydrochloride with the yield of 95.8 percent, and carrying out HPLC:99.76%.

Example 4

Under the protection of argon, adding [ Cp ] IrCl ₂]₂ (0.40 g,0.0005 mol), potassium carbonate (0.69 g,0.005 mol), N-methyl-1-naphthylmethylamine (17.12 g,0.10 mol), p-tert-butyl benzyl alcohol (16.42 g,0.10 mol) and toluene (150 mL) into a Schlenk device, sealing and placing into an oil bath with the temperature of 130 ℃ for reaction for 10 hours, cooling the reaction liquid to room temperature after the reaction is finished, adding dichloromethane (50 mL multiplied by 3) for extraction, merging the extract liquid and concentrating to dryness under reduced pressure, adding HCl/methanol (150 mL,2 mol/L) for salifying, continuously stirring and crystallizing for 2-3 hours, filtering, decompressing and drying a filter cake to obtain the butenafine hydrochloride, wherein the yield is 90.9 percent: 99.75%.

Example 5

Under the protection of argon, adding [ Cp ] IrCl ₂]₂ (3.98 g,0.005 mol), sodium bicarbonate (0.42 g,0.005 mol), N-methyl-1-naphthylmethylamine (17.12 g,0.10 mol), p-tert-butyl benzyl alcohol (16.42 g,0.10 mol) and deionized water (150 mL) into a Schlenk device, sealing and placing the device into an oil bath with a temperature of 110 ℃ for reaction for 5 hours, cooling the reaction liquid to room temperature after the reaction is finished, adding dichloromethane (50 mL multiplied by 3) for extraction, merging the extract liquid for decompression concentration to dryness, adding HCl/isopropanol (150 mL,2 mol/L) for salifying, continuously stirring and crystallizing for 2-3 hours, filtering, decompressing and drying a filter cake to obtain butenafine hydrochloride with a yield of 92.6%, and carrying out HPLC:99.73%.

Example 6

Under the protection of argon, adding [ Cp ] IrI ₂]₂ (2.32 g,0.002 mol), triethylamine (0.51 g,0.005 mol), N-methyl-1-naphthylmethylamine (17.12 g,0.10 mol), p-tert-butyl benzyl alcohol (16.42 g,0.10 mol) and deionized water (150 mL) into a Schlenk device, sealing and placing the device into an oil bath with the temperature of 110 ℃ until the reaction is carried out for 7 hours, cooling the reaction liquid to room temperature after the reaction is finished, adding dichloromethane (50 mL multiplied by 3) for extraction, merging the extract liquid, concentrating the extract liquid under reduced pressure until the extract liquid is dried, adding HCl/ethanol (150 mL,2 mol/L) for salifying, continuously stirring and crystallizing for 2-3 hours, filtering, decompressing and drying a filter cake to obtain butenafine hydrochloride, wherein the yield is 95.8 percent: 99.84%.

Example 7

Under the protection of argon, adding [ Cp ] IrCl ₂]₂ (1.59 g, 0.002mol), sodium bicarbonate (0.084 g,0.001 mol), N-methyl-1-naphthylmethylamine (17.12 g,0.10 mol), p-tert-butyl benzyl alcohol (16.42 g,0.10 mol) and deionized water (150 mL) into a Schlenk device, sealing and placing the device into an oil bath with a temperature of 110 ℃ for reaction for 9 hours, cooling the reaction liquid to room temperature after the reaction is finished, adding ethyl acetate (50 mL multiplied by 4) for extraction, merging the extract liquid for decompression concentration to dryness, adding HCl/ethyl acetate (150 mL,2 mol/L) for salifying, continuously stirring and crystallizing for 2-3 hours, filtering, decompressing and drying a filter cake to obtain the butenafine hydrochloride with the yield of 90.1 percent, and performing HPLC:99.75%.

Example 8

Under the protection of argon, adding [ Cp ] IrCl ₂]₂ (1.59 g, 0.002mol), sodium bicarbonate (0.84 g,0.01 mol), N-methyl-1-naphthylmethylamine (17.12 g,0.10 mol), p-tert-butyl benzyl alcohol (16.42 g,0.10 mol) and deionized water (150 mL) into a Schlenk device, sealing and placing the device into an oil bath with a temperature of 110 ℃ for reaction for 6 hours, cooling the reaction liquid to room temperature after the reaction is finished, adding chloroform (50 mL multiplied by 3) for extraction, merging the extract liquid for decompression concentration to dryness, adding HCl/methanol (150 mL,2 mol/L) for salifying, continuously stirring and crystallizing for 2-3 hours, filtering, decompressing and drying a filter cake to obtain butenafine hydrochloride, wherein the yield is 89.2 percent: 99.72%.

Example 9

Under the protection of argon, rhCl (PPh ₃)₃ (1.85 g,0.002 mol), N-methyl-1-naphthylmethylamine (17.12 g,0.10 mol), p-tert-butyl benzyl alcohol (16.42 g,0.10 mol) and 1, 4-dioxane (150 mL) are added into a stainless steel reaction kettle, the mixture is placed in an oil bath with the temperature of 150 ℃ in a sealing way until the reaction is carried out for 5 hours, after the reaction is finished, the reaction liquid is cooled to room temperature, dichloromethane (50 mL multiplied by 3) is added for extraction, the combined extract is decompressed and concentrated to dryness, HCl/methanol (150 mL,2 mol/L) is added for salifying, the mixture is continuously stirred and crystallized for 2 to 3 hours and then filtered, and a filter cake is decompressed and dried to obtain butenafine hydrochloride with the yield of 94.5 percent and the HPLC of 99.85 percent.

Example 10

RhH (PPh ₃)₄ (2.31 g,0.002 mol), N-methyl-1-naphthylmethylamine (17.12 g,0.10 mol), p-tert-butyl benzyl alcohol (16.42 g,0.10 mol) and acetonitrile (150 mL) are added into a Schlenk device under the protection of argon gas, the mixture is placed into an oil bath with the temperature of 120 ℃ for 6 hours in a sealing way, after the reaction is finished, the reaction solution is cooled to room temperature, dichloromethane (50 mL multiplied by 3) is added for extraction, the combined extract is concentrated to dryness under reduced pressure, HCl/methanol (150 mL,2 mol/L) is added for salifying, the mixture is filtered after continuous stirring crystallization for 2-3 hours, and a filter cake is dried under reduced pressure, thus obtaining butenafine hydrochloride with the yield of 96.1% and the HPLC of 99.81%.

Example 11

Under the protection of argon, adding [ Cp ] IrCl ₂]₂ (1.59 g, 0.002mol), sodium bicarbonate (0.42 g,0.005 mol), N-methyl-1-naphthylmethylamine (17.12 g,0.10 mol), p-tert-butyl benzyl alcohol (16.42 g,0.10 mol) and benzene (150 mL) into a Schlenk device, sealing and placing the device into an oil bath with the temperature of 110 ℃ for reaction for 8 hours, cooling the reaction liquid to room temperature after the reaction is finished, adding dichloromethane (50 mL multiplied by 3) for extraction, merging the extract liquid and concentrating the extract liquid to dryness under reduced pressure, adding HCl/methanol (150 mL,2 mol/L) for salifying, continuously stirring and crystallizing for 2-3 hours, filtering, decompressing and drying a filter cake to obtain butenafine hydrochloride with the yield of 94.2 percent, and carrying out HPLC:99.87%.

Example 12

Under the protection of argon, adding [ Cp ] IrCl ₂]₂ (1.59 g, 0.002mol), sodium bicarbonate (0.42 g,0.005 mol), N-methyl-1-naphthylmethylamine (17.12 g,0.10 mol), p-tert-butyl benzyl alcohol (16.42 g,0.10 mol) and xylene (150 mL) into a glass tube, sealing the tube, placing into an electric furnace with a temperature of 140 ℃ for reaction for 5 hours, cooling the reaction liquid to room temperature after the reaction is finished, adding dichloromethane (50 mL multiplied by 3) for extraction, merging the extract liquid and concentrating the extract liquid to dryness under reduced pressure, adding HCl/methanol (150 mL,2 mol/L) for salifying, continuously stirring and crystallizing for 2-3 hours, filtering, decompressing and drying a filter cake to obtain butenafine hydrochloride with a yield of 95.4 percent, and carrying out HPLC:99.85%.

Claims

1. The synthesis method of butenafine hydrochloride is characterized in that N-methyl-1-naphthylmethylamine and p-tert-butyl benzyl alcohol react to obtain butenafine hydrochloride, and the reaction formula is as follows:

；

The method specifically comprises the following steps: under the protection of inert gas, adding a catalyst, N-methyl-1-naphthylmethylamine, p-tert-butyl benzyl alcohol and a reaction solvent into a sealing device, placing the sealing device into heating equipment with the temperature of 100-150 ℃ for sealing and controlling the temperature until the reaction is finished, extracting by an extracting agent, concentrating an extracting solution under reduced pressure, forming hydrochloride by an HCl/organic solvent, filtering, and drying a filter cake under reduced pressure to obtain butenafine hydrochloride;

The catalyst is as follows: a combination of one of [ Cp IrI ₂]₂ or [ Cp IrCl ₂]₂ with one or a combination of a base of NaHCO ₃、Na₂CO₃、K₂CO₃, acONa, TEA, or RhCl (one of PPh ₃)₃,RhH(PPh₃)₄).

2. The method for synthesizing butenafine hydrochloride according to claim 1, wherein the base is NaHCO ₃.

3. The method for synthesizing butenafine hydrochloride according to claim 1, wherein the molar ratio of N-methyl-1-naphthylmethylamine to p-tert-butyl benzyl alcohol is 1:1.0 to 1.1.

4. The method for synthesizing butenafine hydrochloride according to claim 1, wherein the molar ratio of the N-methyl-1-naphthylmethylamine, cp-Ir complex catalyst, and base is 1:0.5% -5%: 1 to 10 percent.

5. The method for synthesizing butenafine hydrochloride according to claim 1, wherein the molar ratio of the N-methyl-1-naphthylmethylamine to the Rh complex catalyst is 1:0.5 to 5 percent.

6. The method for synthesizing butenafine hydrochloride according to claim 1, wherein the reaction solvent is one or a combination of deionized water, benzene, toluene, xylene, 1, 4-dioxane, acetonitrile.

7. The method for synthesizing butenafine hydrochloride according to claim 1, wherein the reaction solvent is deionized water.

8. The method for synthesizing butenafine hydrochloride according to claim 1, wherein the extraction solvent is one or a combination of dichloromethane, chloroform and ethyl acetate; the HCl/organic solvent is one or a combination of HCl/methanol, HCl/ethanol, HCl/isopropanol, HCl/1, 4-dioxane and HCl/ethyl acetate.