Method for preparing D-galactosamine and hydrochloride thereof

Abstract

The invention belongs to the technical field of medical chemistry, and relates to a novel method for preparing D-galactosamine and hydrochloride thereof. According to the method, a compound shown as a formula I is used as a starting raw material, and the D-galactosamine hydrochloride is finally prepared through condensation, alcoholysis, secondary condensation, acylation, cyclization, deprotection, acidolysis and other multi-step reactions. The selected raw materials are easy to obtain, expensive chemical reagents are not needed, and the production cost is remarkably reduced; reaction conditions are mild, requirements on equipment are low, and operation is simple, convenient and feasible; the whole preparation process does not need column chromatography purification, product purification can be achieved through simple post-treatment means such as crystallization and extraction, and the obtained product is high in purity (the purity can reach 99.0% or above through detection), high in yield (the total yield can reach 45% or above), good in safety and suitable for industrial large-scale production.

Description

Technical Field

[0001] This invention relates to the pharmaceutical field, and specifically to a method for preparing D-galactosamine hydrochloride. Background Technology

[0002] D-galactosamine hydrochloride is a potent inhibitor of hepatic RNA synthesis, capable of persistently damaging hepatocytes. It increases the adhesion of polymorphonuclear leukocytes to hepatic endothelial cells and induces superoxide production. It can also be used to study the pathogenesis of liver diseases, aging, and related conditions, as well as for drug screening. Currently, existing methods for preparing D-galactosamine hydrochloride have many shortcomings and are difficult to meet the needs of industrial production.

[0003] Patent CN1036386A discloses a method for preparing D-aminogalactosamine hydrochloride, which uses chondroitin sulfate as raw material, and obtains D-aminogalactosamine hydrochloride by strong acid high-temperature hydrolysis, chromatography purification, concentration and crystallization. This method has a low yield (mass yield 8.2%), the purification process is cumbersome, requires multiple chromatography, the operation is complicated and the cost is high, making it unsuitable for large-scale industrial production.

[0004] Using tagatose as a starting material, it is condensed with benzylamine to generate N-benzyl-D-tagatoseamine, which is then isomerized in methanol under acidic conditions to generate N-benzyl-D-galactosamine. Finally, it undergoes debenzylation with Pd / C hydrogen and salt formation with hydrochloric acid to prepare D-galactosamine hydrochloride. Although this method is short, it involves intramolecular Heyns rearrangement, making product purification difficult. Furthermore, the use of a Pd / C catalyst presents challenges such as high cost, difficult recovery, and potential heavy metal residue risks.

[0005] The report describes the synthesis of D-galactosamine from D-glucosamine hydrochloride using sodium benzoate and trimethylsulfonic acid, followed by isomerization to D-galactosamine hydrochloride. However, this method is only suitable for small-scale laboratory preparation of D-galactosamine hydrochloride and cannot be scaled up for industrial production.

[0006] Therefore, developing a method for preparing D-galactosamine hydrochloride that uses readily available raw materials, is inexpensive, has mild reaction conditions, is easy to operate, produces easily purified products, and is suitable for industrial production has become an urgent technical problem to be solved in this field. Summary of the Invention

[0007] The purpose of this invention is to overcome the shortcomings of existing methods for preparing D-galactosamine hydrochloride, such as low yield, difficult purification, high cost, and unsuitability for industrial production, and to provide a new method for preparing D-galactosamine and its hydrochloride. This method uses readily available raw materials, operates under mild reaction conditions, is convenient, produces easily purified products, and achieves high yield and purity, making it suitable for large-scale industrial production. To achieve the above objective, this invention provides a method for preparing D-galactosamine hydrochloride, characterized by preparation from compound formula VII as a raw material, with the specific steps as follows:

[0008]

[0009] The reaction is carried out under acidic conditions, with a molar ratio of compound VII to acid of 1:(1.5 ~ 3); the solvent for the reaction is water, and the reaction temperature is 80 ~ 120℃.

[0010] Furthermore, the molar ratio of compound VII to acid is 1:2.3, the acid is hydrochloric acid, the concentration of hydrochloric acid is preferably 3M, and the reaction temperature is 95~100℃.

[0011] Specifically, the reaction involves adding compound VII to 3N hydrochloric acid, heating to 95-100°C and stirring for 18-20 hours under controlled temperature; it may further include a post-treatment step: cooling the reaction solution, filtration, concentration, adding the precipitated crystals, and drying to obtain D-galactosamine hydrochloride.

[0012] The preparation method described above is characterized in that compound VII is prepared from compound VI as a raw material, and the specific steps are as follows:

[0013]

[0014] The reaction is carried out under alkaline conditions, with a molar ratio of compound VI to base of 1:(0.15~0.5); the solvent is an organic solvent; and the reaction temperature is 40~70℃.

[0015] Furthermore, the molar ratio of compound VI to the base is 1:0.25, the base is an inorganic base selected from one or more of sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium carbonate, sodium carbonate, lithium tert-butoxide, and potassium tert-butoxide, preferably sodium methoxide; the organic solvent is selected from one or more of methanol, ethanol, n-propanol, isopropanol, and tert-butanol; the alcohol is more preferably methanol; the reaction temperature is 50-60°C, preferably 55-60°C.

[0016] Specifically, the reaction involves adding compound VI to methanol, adding sodium methoxide, heating to 50-55°C, and reacting for 5-6 hours; it may further include a post-processing step: cooling the reaction solution, crystallizing, filtering, and drying to obtain compound VII.

[0017] The preparation method described above is characterized in that compound VI is prepared from compound V as a raw material, and the specific steps are as follows:

[0018]

[0019] In formula V, R is selected from methanesulfonyl, p-nitrobenzoic acid acyl, trifluoromethanesulfonyl, benzenesulfonyl, p-toluenesulfonyl, preferably trifluoromethanesulfonyl.

[0020] The reaction is carried out under alkaline conditions, the molar ratio of compound V to base is 1:(1.5~2.5); the reaction solvent is an organic solvent; and the reaction temperature is 60~80℃.

[0021] Further, the molar ratio of compound V to the base is 1:2, and the base is an organic base, preferably one or more of the following: monomethylamine, dimethylamine, trimethylamine, monoethylamine, diethylamine, triethylamine, n-propylamine, di-n-propylamine, tri-n-propylamine, isopropylamine, diisopropylamine, triisopropylamine, n-butylamine, N,N-diisopropylethylamine, monoethanolamine, diethanolamine, triethanolamine, ethylenediamine, 1,2-propanediamine, hexamethylenediamine, cyclohexanediamine, benzylamine, phenethylamine, pyridine, 1,8-diazabicycloundec-7-ene (DBU), 1,5-diazabicyclonon-5-ene (DBN), with pyridine being preferred; the organic solvent is selected from dichloromethane, chloroform, 1,2-dichloroethane, with 1,2-dichloroethane being preferred; the reaction temperature is 68~72℃.

[0022] Specifically, the reaction involves adding compound V to 1,2-dichloroethane and water, adding pyridine, heating to 68-72°C, and reacting for 5-6 hours. It may further include a post-treatment step: cooling the reaction solution, adding acid to adjust the pH, extraction, collecting the organic phase, drying and filtering, concentrating under reduced pressure, and drying again. The acid is 2N hydrochloric acid, and the pH value is preferably 0.5-1.5.

[0023] The preparation method described above is characterized in that the compound V is prepared by condensation of compound IV with an acylating agent in the presence of a base, and the specific steps are as follows;

[0024]

[0025] Wherein, R is selected from methanesulfonyl, trifluoromethanesulfonyl, benzenesulfonyl, p-toluenesulfonyl, preferably trifluoromethanesulfonyl.

[0026] Wherein, the molar ratio of compound IV to acylation reagent is 1:(0.9 ~ 1.5); the molar ratio of compound IV to base is 1:(1.5 ~ 2.5); the solvent for the reaction is an organic solvent; the reaction temperature is -20 ~ 0℃;

[0027] Furthermore, according to the preparation method of claim 11, the molar ratio of compound IV to the acylation reagent is 1:1.1, and the acylation reagent is methanesulfonyl chloride, trifluoromethanesulfonyl chloride, trifluoromethanesulfonic anhydride, benzenesulfonyl chloride, p-toluenesulfonyl chloride, preferably trifluoromethanesulfonic anhydride; the molar ratio of compound IV to the base is 1:2.3, and the base is an organic base selected from one or more of pyridine, triethylamine, diisopropylethylamine, DBU, DBN, and ammonia water, preferably pyridine; the organic solvent is selected from dichloromethane, chloroform, 1,2-dichloroethane, preferably dichloromethane; and the reaction temperature is -10°C.

[0028] Specifically, the reaction involves adding compound IV to dichloromethane, cooling to -10°C, adding pyridine and trifluoromethanesulfonic anhydride, and reacting for 3 to 5 hours. It may further include a post-treatment step: cooling the reaction solution, quenching with water, adjusting the pH with acid, extraction, collecting the organic phase, drying and filtering, adding n-heptane to crystallize, and drying. The acid is 2N hydrochloric acid, and the pH value is preferably 0.5 to 1.5.

[0029] The preparation method described above is characterized in that the compound of formula IV is prepared by the following steps:

[0030] (1) Compound I undergoes a condensation reaction with benzoyl chloride in the presence of a base to give compound II:

[0031] (2) Compound II reacts in a methanol solution of hydrogen chloride to give compound III;

[0032] (3) Compound III undergoes a condensation reaction with pivaloyl chloride under alkaline conditions to obtain compound IV.

[0033]

[0034] The preparation method described above is characterized in that: in step (1), the molar ratio of compound formula I to acylation reagent is 1:(0.9 ~ 1.3); the molar ratio of compound formula I to base is 1:(0.8 ~ 1.2); the solvent for the reaction is an organic solvent or a mixed solution of organic solvent and water; the reaction temperature is -10 ~ 10℃;

[0035] Furthermore, in step (1), the molar ratio of compound I to the acylation reagent is 1:1.1; the molar ratio of compound I to the base is 1:1; the solvent for the reaction is a mixed solution of 1,4-dioxane and water; and the reaction temperature is -5 ~ 0℃.

[0036] Step (1) includes: dissolving compound I in 1,4-dioxane and water, cooling to -5°C, adding NaOH, K2CO3 and benzoyl chloride, and reacting for 2 to 3 hours; it may further include a post-treatment step: adding acid to adjust the pH, concentrating under reduced pressure, and drying; the acid is 6N hydrochloric acid, and the pH value is preferably 6 to 7.

[0037] In step (2), the concentration of the hydrogen chloride methanol solution is 0.5% - 1.5%, the molar ratio of compound II to hydrogen chloride is 1: (0.2 ~ 0.5), and the reaction temperature is 60 ~ 80℃;

[0038] Furthermore, in step (2), the concentration of the hydrogen chloride methanol solution is 1%; the reaction temperature is 10 ~ 15℃;

[0039] Step (2) includes: adding compound II to a 1% hydrogen chloride methanol solution, heating to 65-70°C, and reacting for 10-12 hours; and may further include post-processing steps: cooling, crystallization, filtration, and drying.

[0040] In step (3), the molar ratio of compound III to terbinyl chloride is 1:(1.7 ~ 2.5), the molar ratio of compound III to base is 1:(12 ~ 18), the solvent for the reaction is an organic solvent, and the reaction temperature is -30 ~ 0℃.

[0041] Furthermore, in step (3), the molar ratio of compound formula III to terbinyl chloride is 1:2.1; the molar ratio of compound formula III to base is 1:15, the base is an organic base selected from one or more of pyridine, triethylamine, and diisopropylethylamine, preferably pyridine; the organic solvent is selected from dichloromethane, chloroform, and 1,2-dichloroethane, preferably dichloromethane; the reaction temperature of the condensation reaction is preferably -15 ~ -10℃.

[0042] Step (3) includes: dissolving compound III in dichloromethane, cooling to -10 to -15°C, adding pyridine and terbinyl chloride, and reacting for 1.5 to 2 hours; it may further include post-treatment steps: quenching with water, adjusting pH with acid, extraction, concentration, adding n-heptane to crystallize, filtration, and drying; the acid is 6N hydrochloric acid, and the pH value is preferably 0.5 to 1.5.

[0043] This invention provides a method for preparing D-galactosamine hydrochloride, characterized by comprising the following steps:

[0044]

[0045] R is selected from methanesulfonyl, trifluoromethanesulfonyl, benzenesulfonyl, p-toluenesulfonyl, p-nitrobenzoyl, and preferably trifluoromethanesulfonyl.

[0046] Beneficial effects:

[0047] Compared with the prior art, the present invention has the following significant advantages:

[0048] 1. Raw materials are readily available and low in cost: The starting material compound I used in this invention and the reagents required for each step of the reaction are all common chemical raw materials on the market, which are easy to purchase and inexpensive. There is no need to use expensive rare reagents or catalysts (such as Pd / C), which significantly reduces production costs and is suitable for large-scale industrial production.

[0049] 2. Mild reaction conditions and simple operation: The reaction temperature of each step is controlled within the range of -30~120℃, with no extreme high or low temperature requirements. The requirements for equipment materials are low, and conventional enamel-lined reactors can meet the production needs. There are no complicated operation steps during the reaction process. The post-processing mainly adopts simple unit operations such as crystallization, extraction, filtration, and drying, which are easy to master and scale up industrially.

[0050] 3. No column chromatography purification required, resulting in high production efficiency: The entire preparation process does not require complex and time-consuming purification methods such as column chromatography. By optimizing reaction conditions and post-processing, product purification can be achieved with simple operations such as crystallization and extraction, which greatly shortens the production cycle, improves production efficiency, and reduces labor intensity and production costs.

[0051] 4. High product yield and high purity: This invention effectively suppresses side reactions and improves reaction selectivity and conversion rate by optimizing process parameters such as material ratios, reaction temperature, and reaction time in each reaction step. Experimental verification shows that the method of this invention can achieve a total yield of over 45% and a purity of over 99.0% in the preparation of D-galactosamine hydrochloride, which is far superior to the existing technology level and can meet the demand for high-purity products in the pharmaceutical and scientific research fields.

[0052] 5. High safety and environmental friendliness: The reagents used in this invention are highly safe, and no highly toxic, flammable or explosive substances are generated during the reaction process. Furthermore, by optimizing solvent selection and post-processing, the amount and emissions of organic solvents are reduced, thereby reducing environmental pollution and conforming to the concept of green chemical production. Detailed Implementation

[0053] The following detailed description of specific embodiments further illustrates the above-mentioned content of the present invention, but should not be construed as limiting the scope of protection of the present invention in any way. All technical solutions implemented based on the above-mentioned content of the present invention fall within the scope of the present invention. The present invention provides a general and / or specific description of the materials and test methods used in the experiments. Those skilled in the art will understand that, unless otherwise specified, the operations performed in the present invention are conducted under conventional room temperature conditions, which have a technically known meaning in the art, generally referring to 10-30°C, preferably 15-25°C, and more preferably 20-25°C.

[0054] Example 1: Preparation of Compound Formula II

[0055]

[0056] 50g of compound I was added to 200g of water and 150g of dioxane, followed by 9.3g of NaOH, 32g of potassium carbonate, and 35.85g of benzoyl chloride. The reaction was carried out at -5 to 0℃ for 2 to 3 hours. After the reaction was complete, hydrochloric acid was added dropwise to adjust the pH, and then the mixture was concentrated under reduced pressure until a large amount of solid precipitated. The mixture was then cooled to allow crystallization to proceed for 2 to 3 hours. The crystals were filtered, the filter cake was washed with water, and dried to obtain 63.9g of solid (97% yield).

[0057]

[0058] Example 2: Preparation of Compound III

[0059]

[0060] 63.9 g of compound II was added to 280 g of hydrogen chloride methanol solution, heated to 60-70 °C, reacted for 10-12 h, cooled to 0-5 °C, crystallized, filtered, and 58.56 g of compound III was obtained (yield 88%).

[0061]

[0062] Example 3: Preparation of Compound IV

[0063]

[0064] Under nitrogen protection, 58.56 g of compound III was added to a mixture of 234 g pyridine and 58.6 g dichloromethane. After cooling to -10 °C, 49.87 g of pivaloyl chloride was added dropwise. After the addition was complete, the reaction was allowed to proceed at -10 °C for 1.5–2 h. The reaction was then quenched with ice water, and the pH was adjusted with hydrochloric acid. The mixture was extracted with dichloromethane, and the organic phases were combined. The organic phases were washed with water and saturated sodium bicarbonate solution, respectively, and dried over anhydrous sodium sulfate. After concentration under reduced pressure, n-heptane was added. Further concentration under reduced pressure resulted in the precipitation of a small amount of solid. The mixture was then cooled to 0–5 °C, stirred to induce crystallization, filtered, and the filter cake was washed with n-heptane and dried to obtain 68.8 g of compound IV (75% yield).

[0065] .

[0066] Example 4: Preparation of compound V

[0067]

[0068] 68.8 g of compound IV was added to 344 g of dichloromethane, and the mixture was cooled to -15 to -10 °C. Then, 27.5 g of pyridine and 45.86 g of trifluoromethanesulfonic anhydride were added. After the reaction was complete, the mixture was quenched with ice water, and the pH was adjusted with hydrochloric acid. The mixture was extracted with dichloromethane, and the organic phases were combined. The organic phases were washed with water and saturated sodium bicarbonate, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and then n-heptane was added. The mixture was cooled to crystallize, filtered, and the filter cake was washed with n-heptane. The resulting compound V was used directly in the next reaction.

[0069] .

[0070] Example 5: Preparation of compound formula VI

[0071]

[0072] Compound V was added to 275 g of dichloroethane and 137 g of water, followed by 24 g of pyridine. The reaction mixture was heated to 70-72 °C and reacted for 5-6 h. After the reaction was complete, the temperature was lowered, the pH was adjusted to acidic with hydrochloric acid, and the mixture was stirred. The organic phase was collected, and the aqueous phase was extracted with dichloromethane. The organic phases were combined and washed with water and saturated sodium bicarbonate solution, respectively. The organic phase was collected, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain compound VI, which was used directly in the next step.

[0073]

[0074] Example 6: Preparation of compound formula VII

[0075]

[0076] 275.2 g of methanol was added to compound VI, followed by 2.1 g of sodium methoxide. The mixture was heated to 50-55 °C and reacted for 5-6 h. After the reaction was completed, the mixture was cooled, crystallized, filtered, and dried to obtain 28.26 g of compound VII (64% yield).

[0077]

[0078] .

[0079] Example 7: Preparation of compound D-galactosamine hydrochloride

[0080]

[0081] 28.26 g of compound VII was added to 85 g of 3N hydrochloric acid. The reaction solution was heated to 95-100 °C and maintained at this temperature for approximately 18 h. After the reaction was completed, the solution was cooled to 0-5 °C and maintained at this temperature for 2 h. The solid was then filtered off. The filtrate was decolorized by heating activated carbon to 50 °C for 1 h, followed by hot filtration. The filtrate was concentrated under reduced pressure, cooled, and filtered to obtain 21.36 g of D-galactosamine hydrochloride. After drying, 16.12 g of a white solid was obtained (yield 79%).

[0082]

[0083]

Claims

1. A method for preparing D-galactosamine hydrochloride, characterized in that, Prepared from compound formula VII, wherein the amino protection is not limited to one of trifluoroacetyl, benzoyl, benzyloxycarbonyl, tert-butoxycarbonyl, phthaloyl, p-toluenesulfonyl, 2,4-dimethoxybenzyl, p-methoxybenzyl, and benzyl, with benzoyl being preferred. The specific steps are as follows:

2. The preparation method according to claim 1, wherein the reaction is carried out under acidic conditions, the molar ratio of compound VII to acid is 1:(1.5-3); the solvent for the reaction is water, and the reaction temperature is 80-120℃.

3. The preparation method according to claim 2, wherein the molar ratio of compound VII to acid is 1:2.3, the acid is hydrochloric acid, the concentration of hydrochloric acid is preferably 3M, and the reaction temperature is 95-100℃.

4. The preparation method according to claims 1 to 3, characterized in that, Compound VII is prepared from compound VI as a raw material, and the specific steps are as follows:

5. The preparation method according to claim 4, wherein the reaction is carried out under alkaline conditions, the molar ratio of compound VI to base is 1:(0.15-0.5); the solvent is an organic solvent; and the reaction temperature is 40-70°C.

6. The preparation method according to claim 5, characterized in that, The molar ratio of compound VI to the base is 1:0.25, wherein the base is an inorganic base selected from one or more of sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium carbonate, sodium carbonate, lithium tert-butoxide, and potassium tert-butoxide, preferably sodium methoxide; the organic solvent is selected from one or more of methanol, ethanol, and tert-butanol, preferably methanol; and the reaction temperature is 50-55°C.

7. The preparation method according to claims 4 to 6, characterized in that, Compound VI is prepared from compound V as a raw material, and the specific steps are as follows: R is selected from methanesulfonyl, trifluoromethanesulfonyl, benzenesulfonyl, p-toluenesulfonyl, p-nitrobenzoic acid acyl, preferably trifluoromethanesulfonyl.

8. The preparation method according to claim 7, wherein the reaction is carried out under alkaline conditions, the molar ratio of compound V to base is 1:(1.5-2.5); the reaction solvent is an organic solvent; and the reaction temperature is 60-80°C.

9. The preparation method according to claim 8, wherein the molar ratio of compound V to base is 1:2, the base is an organic base selected from one or more of pyridine, triethylamine, and diisopropylethylamine, preferably pyridine; the organic solvent is selected from dichloromethane, chloroform, and 1,2-dichloroethane, preferably 1,2-dichloroethane; and the reaction temperature is 68–72 °C.

10. The preparation method according to claims 7-9, characterized in that, The compound V is prepared by condensation of compound IV with an acylating agent in the presence of a base, as follows: Wherein, R is selected from methanesulfonyl, trifluoromethanesulfonyl, benzenesulfonyl, p-toluenesulfonyl, preferably trifluoromethanesulfonyl.

11. The preparation method according to claim 10, wherein the molar ratio of compound IV to acylation reagent is 1:(0.9-1.5); the molar ratio of compound IV to base is 1:(1.5-2.5); the solvent for the reaction is an organic solvent; and the reaction temperature is -20 to 0°C.

12. The preparation method according to claim 11, wherein the molar ratio of compound IV to the acylation reagent is 1:1.1, and the acylation reagent is methanesulfonyl chloride, trifluoromethanesulfonyl chloride, trifluoromethanesulfonic anhydride, benzenesulfonyl chloride, p-toluenesulfonyl chloride, preferably trifluoromethanesulfonic anhydride; the molar ratio of compound IV to the base is 1:2.3, and the base is an organic base selected from pyridine, triethylamine, diisopropylethylamine, 1,8-diazabicycloundec-7-ene (DBU), 1,5-diazabicyclonon-5-ene (DBN), and ammonia water, preferably pyridine; the organic solvent is selected from dichloromethane, chloroform, 1,2-dichloroethane, preferably dichloromethane; and the reaction temperature is -10°C.

13. The preparation method according to claims 10-12, characterized in that, The compound formula IV was prepared by the following steps: (1) Compound I undergoes a condensation reaction with benzoyl chloride in the presence of a base to give compound II: (2) Compound II reacts in a methanol solution of hydrogen chloride to give compound III; (3) Compound III undergoes a condensation reaction with pivaloyl chloride under alkaline conditions to yield compound IV.

14. The preparation method according to claim 13, characterized in that: In step (1), the molar ratio of compound I to the acylation reagent is 1:(0.9-1.3); the molar ratio of compound I to the base is 1:(0.8-1.2); the solvent for the reaction is an organic solvent or a mixture of organic solvent and water; the reaction temperature is -10 to 10℃. In step (2), the concentration of the hydrochloric acid solution is 0.5%-2.0%, preferably 1.5%, more preferably 1.0%, the molar ratio of compound II to hydrogen chloride is 1:(0.2-0.5), and the reaction temperature is 60-80℃; in step (3), the molar ratio of compound III to pivaloyl chloride is 1:(1.7-2.5), the molar ratio of compound III to base is 1:(12-18), the solvent for the reaction is an organic solvent, and the reaction temperature is -30-0℃.

15. The preparation method according to claim 14, characterized in that: In step (1), the molar ratio of compound formula I to the acylation reagent is 1:1.1; the molar ratio of compound formula I to the base is 1:1; the solvent for the reaction is 1,4-dioxane, acetonitrile, acetone, tetrahydrofuran, ethylene glycol methyl ether, ethylene glycol dimethyl ether and one or more single solvents, or water or a mixture of the above solvents and water, preferably a mixture of 1,4-dioxane and water; the base used in the reaction is one or more combinations of potassium carbonate, sodium carbonate, lithium hydroxide, potassium hydroxide, sodium hydroxide, lithium bicarbonate, potassium bicarbonate, sodium bicarbonate, lithium hydride, potassium hydride, sodium hydride, lithium alkoxide, potassium alkoxide, sodium alkoxide, substituted or unsubstituted alkyl lithium, substituted or unsubstituted amino lithium; the reaction temperature is -10 to 10°C, preferably -5 to 0°C; In step (2), the concentration of the hydrogen chloride alcohol solution is 1%. The hydrogen chloride alcohol solution is not limited to hydrogen chloride methanol solution, hydrogen chloride ethanol solution, hydrogen chloride isopropanol solution, hydrogen chloride tetrahydrofuran solution, hydrogen chloride toluene solution, hydrogen chloride acetone solution, or hydrogen chloride being introduced into one or more of the above-mentioned single solvents, acyl halide methanol solution, acyl halide ethanol solution, acyl halide isopropanol solution, and the acyl halide is one or more of acetyl chloride, benzoyl chloride, oxalyl chloride, chloroacetyl chloride, and trichloroacetyl chloride; the acyl halide is more preferably acetyl chloride. The reaction temperature of the reaction is 30-80°C, preferably 60-80°C, and more preferably 60-70°C. In step (3), the molar ratio of compound formula III to terbinyl chloride is 1:2.1; the molar ratio of compound formula III to base is 1:15, the base is an organic base selected from pyridine, triethylamine, diethylamine, diisopropylethylamine, 1,8-diazabicycloundec-7-ene (DBU), 1,5-diazabicyclonon-5-ene (DBN), and ammonia water, preferably pyridine; the organic solvent is selected from dichloromethane, chloroform, 1,2-dichloroethane, preferably dichloromethane; the reaction temperature of the condensation reaction is preferably -15 to -10℃.

16. A method for preparing D-galactosamine hydrochloride, characterized in that, Includes the following steps: R is selected from methanesulfonyl, trifluoromethanesulfonyl, benzenesulfonyl, p-toluenesulfonyl, p-nitrobenzoic acid acyl, etc., with trifluoromethanesulfonyl being preferred.

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