Preparation method of (S)-(+)-1-methoxy-2-propylamine
By using a substitution reaction between a halogenated reagent and (S)-(+)-2-amino-1-propanol, combined with amino protection and deprotection steps, the high cost and unsuitability for industrialization of existing technologies have been solved, and the preparation of (S)-(+)-1-methoxy-2-propanamine with high yield and low cost has been achieved.
Patent Information
- Application Number
- CN202511097194.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-08-06
- Publication Date
- 2025-11-18
AI Technical Summary
In the existing technology, the synthetic route of (S)-(+)-1-methoxy-2-propane uses expensive Ag2O catalysts and highly toxic methylating agents, resulting in high costs and making it unsuitable for large-scale industrial production.
A halogenated reagent was used to carry out a substitution reaction with (S)-(+)-2-amino-1-propanol, followed by amino protection, etherification and amino deprotection reactions. Relatively inexpensive and safe reagents were used, and the reaction conditions were optimized to improve the yield and reduce the cost.
It achieves mild reaction conditions, a yield of over 95%, is suitable for large-scale industrial production, produces high-purity products, is easy to operate, and is inexpensive.
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Figure CN120965501A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of biochemical pharmaceutical technology, specifically relating to a method for preparing (S)-(+)-1-methoxy-2-propylamine. Background Technology
[0002] Dimethyl phenoxychloride belongs to the chloroacetamide class of herbicides, specifically the amide class. Its main mechanism of action is to inhibit cell division to achieve weed control. It was developed by Syngenta and further developed by BASF. Dimethyl phenoxychloride exists in two configurations, S and R. The active chiral form, dimethyl phenoxychloride, is the optical S configuration of dimethyl phenoxychloride. It requires only 50% of the dosage of the racemic form and has a promising market prospect. Therefore, the synthesis of its intermediate (S)-(+)-1-methoxy-2-propanamine hydrochloride is particularly important.
[0003] (S)-(+)-1-methoxy-2-propane hydrochloride (i.e., compound 1) is an important intermediate for the selective synthesis of dimethinyl chlorpyrifos (i.e., compound 2).
[0004] .
[0005] Patent US8440673B2 reports the following synthetic route for (R)-1-methoxy-2-propylamine: Step 1: Reduce the carboxyl group of D-alanine with LAH, then protect the amino group with Boc anhydride; Step 2: Methylate the hydroxyl group using Ag₂O and MeI; Step 3: Remove the Boc group under acidic conditions. This synthetic route not only uses expensive Ag₂O as a catalyst, but also uses the highly toxic methylating agent MeI, making it costly and toxic, unsuitable for large-scale industrial production. Summary of the Invention
[0006] The purpose of this invention is to overcome the problem of difficulty in large-scale industrial production in the existing technology, and to provide a new method for preparing (S)-(+)-1-methoxy-2-propane. This method has mild reaction conditions, high yield, low cost, is green and environmentally friendly, and is easy to operate, making it easy to achieve industrialization.
[0007] The technical solution of the present invention is as follows: a method for preparing (S)-(+)-1-methoxy-2-propanamine hydrochloride, the method comprising the following steps: The halogenating agent was added dropwise to a mixture of (S)-(+)-2-amino-1-propanol (compound 3) and solvent to carry out a substitution reaction, and the reaction yielded (S)-(+)-2-amino-1-halopropane (compound 4). In a solvent, compound 4, an organic amine reagent, and an amino protecting reagent undergo an amino protection reaction to yield compound 5; In a solvent, compound 5 and methanol were subjected to an etherification reaction to obtain compound 6; In a solvent, compound 6 and an amino deprotecting agent were subjected to a deprotection reaction to give (S)-(+)-1-methoxy-2-propylamine hydrochloride; The reaction process is as follows: .
[0008] Preferably, the molar ratio of compound 3 to the halogenated reagent is 1:1 to 4.
[0009] More preferably, the molar ratio of compound 3 to the halogenated reagent is 1:1.05~2.
[0010] Preferably, the dropping temperature is -10~10℃, the dropping time is 0.2~2 hours, the contact reaction temperature is -10~80℃, and the contact reaction time is 0.5~8 hours.
[0011] More preferably, the dropping temperature is -10~0℃, the dropping time is 0.5~1 hour, the contact reaction temperature is 40~60℃, and the contact reaction time is 2~5 hours.
[0012] Preferably, the halogenated reagent is one or more selected from thionyl chloride, hydrogen chloride, hydrogen bromide, PCl3, PCl5, and PBr3.
[0013] Preferably, the solvent for the substitution reaction is at least one or more of dichloromethane, 1,1-dichloroethane, 1,2-dichloroethane, chloroform, and carbon tetrachloride.
[0014] Preferably, the molar ratio of compound 4 to the amino protecting agent is 1:1 to 2.
[0015] More preferably, the molar ratio of compound 4 to the amino protecting agent is 1:1.05~1.25.
[0016] Preferably, the temperature of the second contact reaction is 0~80℃, and the contact reaction time is 1~8 hours.
[0017] More preferably, the temperature of the second contact reaction is 40~50°C, and the contact reaction time is 3~5 hours.
[0018] Preferably, the amino protecting agent is one or more of benzooxyformyl chloride, ditert-butyl dicarbonate, and fluorenyl chloroformate.
[0019] Preferably, the organic amine reagent can be one or more of triethylamine, diethylpalmitamide, and tripropylamine.
[0020] Preferably, the amino-protected solvent is at least one or more selected from dichloromethane, 1,1-dichloroethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, tetrahydrofuran, 2-methyltetrahydrofuran, and diethyl ether.
[0021] Preferably, the molar ratio of compound 5 to methanol is 1:1 to 4.
[0022] More preferably, the molar ratio of compound 5 to methanol is 1:1.05~1.25.
[0023] Preferably, the alkaline reagent is one or more of sodium hydride, sodium methoxide, potassium methoxide, sodium tert-butoxide, and potassium tert-butoxide.
[0024] Preferably, the molar ratio of compound 5 to the alkaline reagent is 1:1 to 3.
[0025] More preferably, the molar ratio of compound 5 to the alkaline reagent is 1:1.25~1.5.
[0026] Preferably, the etherification reaction temperature is 20~80℃ and the contact reaction time is 0.5~8 hours.
[0027] More preferably, the etherification reaction temperature is 40~60°C, and the contact reaction time is 3~5 hours.
[0028] Preferably, the solvent for the etherification reaction is at least one or more selected from dichloromethane, 1,1-dichloroethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, ethers, cyclic ethers, aromatic hydrocarbons, chloroform, and aliphatic hydrocarbons.
[0029] Preferably, the molar ratio of compound 6 to the amino deprotecting agent is 1:1 to 2.
[0030] More preferably, the molar ratio of compound 6 to the amino deprotecting agent is 1:1.25~1.5.
[0031] Preferably, the temperature of the deprotection reaction is 0~100℃, and the contact reaction time is 0.5~24 hours.
[0032] More preferably, the deprotection reaction temperature is 80~90℃, and the contact reaction time is 3~5 hours.
[0033] Preferably, the amino deprotecting agent is hydrochloric acid.
[0034] Preferably, the deprotecting solvent is at least one or more of the following: water, ethers, cyclic ethers, alcohols, aromatic hydrocarbons, halogenated hydrocarbons, and aliphatic hydrocarbons.
[0035] The method of this invention has mild reaction conditions, high yield, and simple operation. The product purity can reach over 95%, and the yield can reach over 94.5%, making it suitable for large-scale industrial production. Attached Figure Description
[0036] Figure 1 Example 1 yielded (S)-(+)-1-methoxy-2-propylamine hydrochloride. 1 H NMR spectrum. Detailed Implementation
[0037] The endpoints and any values of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values should be understood to include values close to these ranges or values. For numerical ranges, the endpoint values of the various ranges, the endpoint values of the various ranges and individual point values, and individual point values can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.
[0038] Example 1: 4.88 g (0.065 mol, 1 eq.) of compound 3 and 100 g of dichloromethane were added to a reaction flask. The mixture was stirred and cooled to 0 °C. 9.76 g (0.082 mol, 1.25 eq.) of thionyl chloride was slowly added dropwise over 0.5 hours. After the addition was complete, the temperature was slowly raised to 40 °C and maintained for 4 hours. After the reaction was completed, the temperature was cooled to room temperature, and 26.39 g (0.261 mol, 4 eq.) of triethylamine was slowly added to obtain a dichloromethane solution of compound 4.
[0039] 15.71 g (0.072 mol, 1.1 eq.) of (Boc)₂O was added to the flask, stirred and heated to 40 °C, and kept at that temperature for 3 hours to obtain a dichloromethane solution of compound 5.
[0040] The temperature was lowered to 30°C, and 4.59 g (0.085 mol, 1.3 eq.) of sodium methoxide was added. Then, 2.30 g (0.072 mol, 1.1 eq.) of methanol was slowly added dropwise. The temperature was raised to 40°C and kept at that temperature for 5 hours. After the temperature was maintained, the reaction solution was washed three times with 50 ml of water to obtain a dichloromethane solution of compound 6.
[0041] At room temperature, 2.63 g (0.072 mol, 1.1 eq.) of hydrochloric acid was slowly added dropwise to the solution, and the temperature was raised to 40 °C and reacted for 15 hours. The mother liquor was then evaporated by rotary evaporation to obtain 8.09 g of product (S)-(+)-1-methoxy-2-propylamine hydrochloride, with a purity of 95.40% and a yield of 94.54%.
[0042] (S)-(+)-1-methoxy-2-propylamine hydrochloride 1 The H NMR characterization results are shown in [reference]. Figure 1 ,analyze Figure 1 It can be known that: 1 H NMR (400 MHz, CD3CN) δ 8.17 (s, 3H), 3.61 – 3.55 (m, 2H), 3.54 – 3.49 (m, 1H), 3.38 (s, 3H), 1.35 (d, J = 5.7 Hz, 3H).
[0043] Example 2: 4.88 g (0.065 mol, 1 eq.) of compound 3 and 100 g of 1,1-dichloroethane were added to a reaction flask. The mixture was stirred and cooled to 0°C. 8.21 g (0.069 mol, 1.05 eq.) of thionyl chloride was slowly added dropwise over 0.5 hours. After the addition was complete, the temperature was slowly raised to 57°C and maintained for 3 hours. After the reaction was completed, the mixture was cooled to room temperature, and 26.39 g (0.261 mol, 4 eq.) of triethylamine was slowly added to obtain a 1,1-dichloroethane solution of compound 4.
[0044] Add 15.06 g (0.069 mol, 1.05 eq.) of (Boc)2O to the flask, stir and heat to 57 °C, keep warm for 3 hours to obtain a 1,1-dichloroethane solution of compound 5. Wash three times with 50 ml of water and evaporate the solvent to obtain crude compound 5.
[0045] Add 50 g of n-heptane to the crude compound 5, add 5.96 g (0.085 mol, 1.3 eq.) of potassium methoxide, and slowly add 2.62 g (0.082 mol, 1.25 eq.) of methanol dropwise. Heat to 60 °C and maintain the temperature for 3 hours. After the temperature maintenance is completed, wash the reaction solution three times with 50 ml of water, and evaporate the solvent to obtain the crude compound 6.
[0046] After adding the crude compound 6 to a flask, 50 g of water was added, followed by the slow addition of 2.63 g (0.072 mol, 1.1 eq.) of hydrochloric acid. The mixture was heated to 90 °C and reacted for 3 hours. After cooling to room temperature, the mother liquor was evaporated by rotary evaporation to obtain 8.15 g of product (S)-(+)-1-methoxy-2-propylamine hydrochloride, with a purity of 95.10% and a yield of 94.94%.
[0047] Example 3: 4.88 g (0.065 mol, 1 eq.) of compound 3 and 100 g of 1,1-dichloroethane were added to a reaction flask. The mixture was stirred and cooled to 0 °C. 9.82 g (0.082 mol, 1.25 eq.) of thionyl chloride was slowly added dropwise over 0.5 hours. After the addition was complete, the temperature was slowly raised to 57 °C and maintained for 3 hours. After the reaction was completed, the temperature was cooled to room temperature, and 26.6 g (0.261 mol, 4 eq.) of triethylamine was slowly added to obtain a 1,1-dichloroethane solution of compound 4.
[0048] 12.28 g (0.072 mol, 1.1 eq.) of benzooxyformyl chloride was added to the flask, stirred and heated to 57 °C, and kept at that temperature for 3 hours to obtain a 1,1-dichloroethane solution of compound 5.
[0049] The temperature was lowered to 30°C, and 8.17 g (0.085 mol, 1.3 eq.) of sodium tert-butoxide was added. Then, 2.30 g (0.072 mol, 1.1 eq.) of methanol was slowly added dropwise. The temperature was raised to 55°C and kept at that temperature for 4 hours. After the temperature was maintained, the reaction solution was washed three times with 50 ml of water to obtain a 1,1-dichloroethane solution of compound 6.
[0050] At room temperature, 2.63 g (0.072 mol, 1.1 eq.) of hydrochloric acid was slowly added dropwise to the solution, and the temperature was raised to 57 °C and reacted for 8 hours. The mother liquor was then evaporated by rotary evaporation to obtain 8.16 g of product (S)-(+)-1-methoxy-2-propylamine hydrochloride with a purity of 95.08% and a yield of 95.03%.
[0051] Example 4: 4.88 g (0.065 mol, 1 eq.) of compound 3 and 100 g of dichloromethane were added to a reaction flask. The mixture was stirred and cooled to -5°C. 9.76 g (0.082 mol, 1.25 eq.) of thionyl chloride was slowly added dropwise over 0.5 hours. After the addition was complete, the temperature was slowly raised to 40°C and maintained for 5 hours. After the reaction was completed, the temperature was lowered to room temperature, and 37.39 g (0.261 mol, 4 eq.) of tripropylamine was slowly added to obtain a dichloromethane solution of compound 4.
[0052] 15.71 g (0.072 mol, 1.1 eq.) of (Boc)₂O was added to the flask, stirred and heated to 40 °C, and kept at that temperature for 3 hours to obtain a dichloromethane solution of compound 5.
[0053] The temperature was lowered to 30°C, and 9.54 g (0.085 mol, 1.3 eq.) of potassium tert-butoxide was added. Then, 2.30 g (0.072 mol, 1.1 eq.) of methanol was slowly added dropwise. The temperature was raised to 40°C and kept at this temperature for 6 hours. After the temperature was maintained, the reaction solution was washed three times with 50 ml of water to obtain a dichloromethane solution of compound 6.
[0054] At room temperature, 2.63 g (0.072 mol, 1.1 eq.) of hydrochloric acid was slowly added dropwise to the solution, and the temperature was raised to 40 °C and reacted for 15 hours. The mother liquor was then evaporated by rotary evaporation to obtain 8.12 g of product (S)-(+)-1-methoxy-2-propylamine hydrochloride, with a purity of 95.26% and a yield of 94.74%.
[0055] Example 5: 4.88 g (0.065 mol, 1 eq.) of compound 3 and 100 g of carbon tetrachloride were added to a reaction flask. The mixture was stirred and cooled to -5°C. 8.21 g (0.069 mol, 1.05 eq.) of thionyl chloride was slowly added dropwise over 0.5 hours. After the addition was complete, the temperature was slowly raised to 40°C and maintained for 5 hours. After the reaction was completed, the mixture was cooled to room temperature, and 26.39 g (0.261 mol, 4 eq.) of triethylamine was slowly added to obtain a carbon tetrachloride solution of compound 4.
[0056] Add 15.06 g (0.069 mol, 1.05 eq.) of (Boc)₂O to the flask, stir and heat to 45 °C, keep warm for 3 hours to obtain a carbon tetrachloride solution of compound 5.
[0057] The temperature was lowered to 25°C, 2.04 g (0.085 mol, 1.3 eq.) of sodium hydride was added, and 2.62 g (0.082 mol, 1.25 eq.) of methanol was slowly added dropwise. The temperature was raised to 65°C and kept at that temperature for 3 hours. After the temperature was set, the reaction solution was washed three times with 50 ml of water to obtain a carbon tetrachloride solution of compound 6.
[0058] After evaporating the carbon tetrachloride solution of compound 6 by rotary evaporation, 50 g of toluene was added to the flask at room temperature, followed by the slow addition of 2.63 g (0.072 mol, 1.1 eq.) of hydrochloric acid. The mixture was heated to 90 °C and reacted for 4 hours. After cooling to room temperature, the mother liquor was evaporated by rotary evaporation to obtain 8.19 g of product (S)-(+)-1-methoxy-2-propylamine hydrochloride, with a purity of 95.03% and a yield of 95.33%.
[0059] Example 6: 4.88 g (0.065 mol, 1 eq.) of compound 3 and 100 g of 1,2-dichloroethane were added to a reaction flask. The mixture was stirred and cooled to -5°C. 8.21 g (0.069 mol, 1.05 eq.) of thionyl chloride was slowly added dropwise over 0.5 hours. After the addition was complete, the temperature was slowly raised to 60°C and maintained for 3 hours. After the reaction was complete, the mixture was cooled to room temperature, and 26.39 g (0.261 mol, 4 eq.) of triethylamine was slowly added to obtain a 1,2-dichloroethane solution of compound 4.
[0060] Add 15.06 g (0.069 mol, 1.05 eq.) of (Boc)2O to the flask, stir and heat to 45 °C, keep warm for 3 hours to obtain a 1,2-dichloroethane solution of compound 5.
[0061] The temperature was lowered to 25°C, and 4.59 g (0.085 mol, 1.3 eq.) of sodium methoxide was added. Then, 2.62 g (0.082 mol, 1.25 eq.) of methanol was slowly added dropwise. The temperature was raised to 60°C and kept at that temperature for 3 hours. After the temperature was set, the reaction solution was washed three times with 50 ml of water to obtain a 1,2-dichloroethane solution of compound 6.
[0062] After evaporating the 1,2-dichloroethane solution of compound 6 by rotary evaporation, 50 g of water was added to the flask at room temperature, followed by the slow addition of 3.58 g (0.098 mol, 1.5 eq.) of hydrochloric acid. The mixture was heated to 90 °C and reacted for 3 hours. After cooling to room temperature, the mother liquor was evaporated by rotary evaporation to obtain 8.22 g of product (S)-(+)-1-methoxy-2-propylamine hydrochloride, with a purity of 95.11% and a yield of 95.76%.
[0063] Comparative Example 1: (Compared to Example 1, the reaction temperature in step three was changed) 4.88 g (0.065 mol, 1 eq.) of compound 3 and 100 g of dichloromethane were added to the reaction flask. The mixture was stirred and cooled to 0 °C. 9.76 g (0.082 mol, 1.25 eq.) of thionyl chloride was slowly added dropwise over 0.5 hours. After the addition was complete, the temperature was slowly raised to 40 °C and maintained for 5 hours. After the reaction was complete, the temperature was cooled to room temperature, and 26.39 g (0.261 mol, 4 eq.) of triethylamine was slowly added to obtain a dichloromethane solution of compound 4.
[0064] 15.71 g (0.072 mol, 1.1 eq.) of (Boc)₂O was added to the flask, stirred and heated to 40 °C, and kept at that temperature for 3 hours to obtain a dichloromethane solution of compound 5.
[0065] The temperature was lowered to 15°C, and 4.59 g (0.085 mol, 1.3 eq.) of sodium methoxide was added. Then, 2.30 g (0.072 mol, 1.1 eq.) of methanol was slowly added dropwise. The mixture was kept at this temperature for 5 hours. After the incubation was completed, the reaction solution was washed three times with 50 ml of water to obtain a dichloromethane solution of compound 6.
[0066] At room temperature, 2.63 g (0.072 mol, 1.1 eq.) of hydrochloric acid was slowly added dropwise to the solution, and the temperature was raised to 40 °C and reacted for 15 hours. The mother liquor was then evaporated by rotary evaporation to obtain 7.02 g of product (S)-(+)-1-methoxy-2-propylamine hydrochloride, with a purity of 82.30% and a yield of 70.77%.
[0067] Comparative Example 2: (Compared to Example 1, the alkaline reagent in step three was replaced) 4.88 g (0.065 mol, 1 eq.) of compound 3 and 100 g of dichloromethane were added to the reaction flask. The mixture was stirred and cooled to 0 °C. 9.76 g (0.082 mol, 1.25 eq.) of thionyl chloride was slowly added dropwise over 0.5 hours. After the addition was complete, the temperature was slowly raised to 40 °C and maintained for 5 hours. After the reaction was complete, the mixture was cooled to room temperature, and 26.39 g (0.261 mol, 4 eq.) of triethylamine was slowly added to obtain a dichloromethane solution of compound 4.
[0068] 15.71 g (0.072 mol, 1.1 eq.) of (Boc)₂O was added to the flask, stirred and heated to 40 °C, and kept at that temperature for 3 hours to obtain a dichloromethane solution of compound 5.
[0069] The temperature was lowered to 30°C, and 3.40 g (0.085 mol, 1.3 eq.) of sodium hydroxide was added. Then, 2.30 g (0.072 mol, 1.1 eq.) of methanol was slowly added dropwise. The temperature was raised to 40°C and kept at this temperature for 5 hours. After the temperature was maintained, the reaction solution was washed three times with 50 ml of water to obtain a dichloromethane solution of compound 6.
[0070] At room temperature, 2.63 g (0.072 mol, 1.1 eq.) of hydrochloric acid was slowly added dropwise to the solution, and the temperature was raised to 40 °C and reacted for 15 hours. The mother liquor was then evaporated by rotary evaporation to obtain 6.36 g of product (S)-(+)-1-methoxy-2-propylamine hydrochloride, with a purity of 42.63% and a yield of 33.22%.
[0071] Examples 1-6 show that Example 6 has the best effect. Steps one through three use 1,2-dichloroethane as the solvent, and step four uses water as the solvent. In step two, triethylamine is used as the basic substance and di-tert-butyl dicarbonate as the amino protecting agent. In step three, sodium methoxide is used as the basic substance, resulting in the best effect. The optimal reaction temperature is -5°C for step one, 60°C for the holding temperature, 45°C for step two, 60°C for step three, and 90°C for step four. In Comparative Example 1, lowering the reaction temperature in step three leads to a decrease in etherification efficiency within the same time frame, ultimately resulting in a 23.76% decrease in product yield. In Comparative Example 2, in step three, using sodium hydroxide, which is weaker than sodium methoxide, prevents compound 5 from quickly reaching the deprotonated state, leading to a decrease in etherification efficiency and ultimately a 61.31% decrease in product yield.
Claims
1. A method for preparing (S)-(+)-1-methoxy-2-propylamine hydrochloride, characterized in that, The method includes the following steps: The halogenating agent was added dropwise to a mixture of (S)-(+)-2-amino-1-propanol (compound 3) and the first solvent to carry out a substitution reaction, which yielded (S)-(+)-2-amino-1-halopropane (compound 4). In the second solvent, compound 4, an organic amine reagent, and an amino protecting reagent were added sequentially to carry out an amino protection reaction to obtain compound 5; In a third solvent, compound 5, a basic reagent, and methanol are subjected to an etherification reaction to obtain compound 6; In a fourth solvent, compound 6 was mixed with hydrochloric acid and subjected to a deprotection reaction to give (S)-(+)-1-methoxy-2-propylamine hydrochloride; The reaction process is as follows: .
2. The method for preparing (S)-(+)-1-methoxy-2-propylamine hydrochloride according to claim 1, characterized in that: The halogenated reagent in step 1) is one or more of thionyl chloride, hydrogen chloride, hydrogen bromide, PCl3, PCl5, and PBr3; the first solvent is one or more of dichloromethane, 1,1-dichloroethane, 1,2-dichloroethane, chloroform, and carbon tetrachloride; the molar ratio of the halogenated reagent to compound 3 is (1~4):
1.
3. The method for preparing (S)-(+)-1-methoxy-2-propylamine hydrochloride according to claim 1, characterized in that: In step 2), the second solvent is one or more of dichloromethane, 1,1-dichloroethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, tetrahydrofuran, 2-methyltetrahydrofuran, and diethyl ether; the organic amine reagent is one or more of triethylamine, diethylpalmitamide, and tripropylamine; the amino protecting reagent in step 2) is one or more of benzoxyformyl chloride, ditert-butyl dicarbonate, and 9-fluorenyl methyl chloroformate; and the molar ratio of compound 4 to the amino protecting reagent is 1:(1~2).
4. The method for preparing (S)-(+)-1-methoxy-2-propylamine hydrochloride according to claim 1, characterized in that: The third solvent in step 3) is one or more of the following: dichloromethane, 1,1-dichloroethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, ethers, cyclic ethers, aromatic hydrocarbons, chloroform, and aliphatic hydrocarbons; the alkaline reagent is one or more of the following: sodium hydride, sodium methoxide, potassium methoxide, sodium tert-butoxide, and potassium tert-butoxide; the molar ratio of compound 5 to methanol is 1:1 to 4; and the molar ratio of compound 5 to the alkaline reagent is 1:1 to 3.
5. The method for preparing (S)-(+)-1-methoxy-2-propylamine hydrochloride according to claim 1, characterized in that: The fourth solvent in step 4) is one or more of the following: water, ethers, cyclic ethers, alcohols, aromatic hydrocarbons, halogenated hydrocarbons, and aliphatic hydrocarbons.
6. The method for preparing (S)-(+)-1-methoxy-2-propylamine hydrochloride according to claim 1, characterized in that: The conditions for the substitution reaction include: a dropping temperature of -10 to 10°C, a dropping time of 0.2 to 2 hours, a reaction temperature of -10 to 80°C, and a reaction time of 0.5 to 8 hours.
7. The method for preparing (S)-(+)-1-methoxy-2-propylamine hydrochloride according to claim 1, characterized in that: The temperature for the amino protection reaction is 0-80℃, and the reaction time is 1-8 hours.
8. The method for preparing (S)-(+)-1-methoxy-2-propylamine hydrochloride according to claim 1 or 2, characterized in that: The etherification reaction is carried out at a temperature of 20~80℃ for 0.5~8 hours.
9. The method for preparing (S)-(+)-1-methoxy-2-propylamine hydrochloride according to claim 1 or 2, characterized in that: The deprotection reaction temperature is 0~100℃, and the reaction time is 0.5~24 hours.