Preparation method of high-purity amino acid benzyl ester hydrochloride

Abstract

The invention relates to the technical field of medicine synthesis, in particular to a preparation method of high-purity amino acid benzyl ester hydrochloride. The high-purity amino acid benzyl ester hydrochloride is prepared by carrying out tert-butoxycarbonyl protection reaction, coupling reaction, tert-butoxycarbonyl deprotection reaction and recrystallization on amino acid. The preparation method provided by the invention does not need to use toxic organic solvent benzene, benzyl alcohol and a catalyst, so that the synthesis cost is saved, a large amount of wastewater is not generated in the synthesis process, the operation flow is simplified, and the synthesis route is safer and more environment-friendly. The method effectively solves the problems that the existing method for synthesizing the amino acid benzyl ester hydrochloride needs to use a toxic solvent, a large amount of wastewater is generated in the synthesis process, impurities are easy to introduce, and the product purity is low, and provides a new thought for synthesis of the high-purity amino acid benzyl ester hydrochloride.

Description

Technical Field

[0001] The invention relates to the technical field of drug synthesis, and in particular to a method for preparing high-purity amino acid benzyl ester hydrochloride. Background Art

[0002] With the development of society, peptides are increasingly used in the fields of medicine, health care products and cosmetics. As the raw materials for synthetic peptides, the research and development of amino acid derivatives is crucial, and amino acid benzyl ester hydrochloride is an important component of amino acid derivatives.

[0003] The existing preparation method of amino acid benzyl ester hydrochloride is to use benzene as solvent, amino acid and benzyl alcohol as raw materials, p-toluenesulfonic acid as catalyst, and obtain amino acid benzyl ester p-toluenesulfonate by reflux of benzene; then obtain amino acid benzyl ester hydrochloride by dissociation, extraction, drying and salt formation. However, this process not only uses benzene with high toxicity as solvent, but also uses N,N-dimethylformamide, a highly polar solvent, to dissociate amino acid benzyl ester p-toluenesulfonate, and needs to be washed with a large amount of water during post-treatment. Therefore, a large amount of wastewater is generated during the dissociation of amino acid benzyl ester p-toluenesulfonate, resulting in high impurity content and poor purity of the product, which cannot meet the requirements of synthetic polypeptides.

[0004] Based on this, developing a high-purity amino acid benzyl ester hydrochloride with a safe and non-toxic preparation process has important practical significance for the synthesis of polypeptides. Summary of the invention

[0005] The existing method for synthesizing amino acid benzyl hydrochloride needs to use toxic solvents, and the synthesis process will produce a large amount of wastewater, which is easy to introduce impurities, resulting in a problem of low product purity. The present invention provides a method for preparing high-purity amino acid benzyl hydrochloride. The present invention first performs Boc protection on the amino acid, then performs a coupling reaction, and finally removes the Boc protecting group by hydrogen chloride gas, and finally obtains the high-purity amino acid benzyl hydrochloride by recrystallization. The preparation method provided by the present invention does not need to use toxic organic solvents, benzyl alcohol and catalysts, saves synthesis costs, and does not produce a large amount of wastewater during the synthesis process, simplifies the operation process, and the synthesis route is safer and more environmentally friendly, which provides a new idea for the synthesis of high-purity amino acid benzyl hydrochloride.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions: The first aspect of the present invention provides a method for preparing high-purity amino acid benzyl ester hydrochloride, comprising the following steps: Step 1: dissolving the amino acid in an organic ester solvent, adding Boc anhydride and a strong base, and performing a tert-butyloxycarbonyl protection reaction to obtain a Boc-amino acid; Step 2, adding benzyl halide to the Boc-amino acid for coupling reaction to obtain Boc-amino acid benzyl ester; Step 3: performing a tert-butyloxycarbonyl deprotection reaction on the Boc-amino acid benzyl ester to obtain high-purity amino acid benzyl ester hydrochloride.

[0007] The present invention firstly adopts a tert-butyloxycarbonyl protection reaction to protect the amino group on the amino acid, thereby reducing the reactivity of the amino group and avoiding the occurrence of side reactions. Due to the existence of the amino group protection, the reaction site between the benzyl halide and the Boc-amino acid is only the carboxyl site of the Boc-amino acid, which greatly reduces the probability of the occurrence of side products, thereby improving the yield and purity of the target product. Finally, the present invention obtains high-purity amino acid benzyl ester hydrochloride through a tert-butyloxycarbonyl deprotection reaction, and the specific reaction process is shown as follows.

[0008]

[0009] Compared with the prior art, the present invention adopts tert-butyloxycarbonyl protection reaction to carry out amino protection to amino acid, adopts organic ester solvent to reach reaction requirement, does not need to use highly toxic organic solvent benzene at all, does not need to use benzyl alcohol and catalyst, saves synthesis cost, makes synthesis process safer and more environmentally friendly. More importantly, in the synthetic route of the present invention, it is not necessary to use large polar solvents throughout the whole process, avoids the operation of washing with a large amount of water in the post-processing process, does not produce a large amount of organic waste water, does not therefore cause product purity to be low, quality declines, and operation is more economical and environmentally friendly. The technical solution of the present invention is used to effectively solve the existing method of synthesizing amino acid benzyl ester hydrochloride, which needs to use toxic solvents, and the synthesis process will produce a large amount of waste water, easily introduce impurities, and cause the problem of low product purity, which provides a new idea for the synthesis of high-purity amino acid benzyl hydrochloride.

[0010] Preferably, the preparation method of high-purity amino acid benzyl ester hydrochloride comprises the following steps: In step 1, the amino acid is dissolved in an organic ester solvent, Boc anhydride and a strong base are added, and a tert-butyloxycarbonyl protection reaction is carried out at 50-70° C., the temperature is lowered to 8-12° C., the solid-liquid separation is performed, the washing is performed, and the drying is performed to obtain a Boc-amino acid; Step 2, adding benzyl halide to the Boc-amino acid, carrying out coupling reaction at 0-20° C., washing, and drying to obtain Boc-amino acid benzyl ester; Step 3: subjecting the Boc-amino acid benzyl ester to tert-butyloxycarbonyl deprotection reaction, solid-liquid separation, and recrystallization of the solid filtrate to obtain high-purity amino acid benzyl ester hydrochloride.

[0011] Preferably, in step 1, the amino acid includes any one of glycine, proline, leucine, phenylalanine, threonine, serine or 2-aminoisobutyric acid.

[0012] Preferably, in step 1, the strong base is sodium hydroxide or potassium hydroxide.

[0013] Preferably, in step 1, the organic ester solvent is any one of ethyl acetate, isopropyl acetate, tert-butyl acetate or methyl acetate.

[0014] Preferably, in step 1, the mass ratio of the amino acid to the organic ester solvent is 1:3-1:4.

[0015] Preferably, in step 1, the molar ratio of the amino acid to the Boc anhydride is 0.6:1-1.8:1.

[0016] Preferably, in step 1, the mass ratio of the amino acid to the strong base is 1:1-1:1.1.

[0017] Preferably, in step 1, the strong base is sodium hydroxide or potassium hydroxide.

[0018] Preferably, in step 1, the tert-butyloxycarbonyl protection reaction time is 9h-12h.

[0019] Preferably, in step 2, the coupling reaction time is 6h-24h.

[0020] Preferably, in step 2, the molar ratio of the Boc-amino acid to the benzyl halide is 1:1-1:2.

[0021] Preferably, in step three, the specific operation of the tert-butyloxycarbonyl deprotection reaction comprises the following steps: introducing hydrogen chloride gas into the Boc-amino acid benzyl ester to carry out the tert-butyloxycarbonyl deprotection reaction.

[0022] Further preferably, in step three, the amount of hydrogen chloride gas introduced is 1 L / min-10 L / min.

[0023] Further preferably, in step 3, the introduction time of the hydrogen chloride gas is 6h-12h.

[0024] Preferably, in step three, the recrystallization temperature is 20°C-30°C, and the recrystallization time is 12h-18h.

[0025] Preferably, in step three, the recrystallization solvent is any one of ethyl acetate, isopropyl acetate, tert-butyl acetate or methyl acetate.

[0026] In summary, the present invention uses amino acid as basic raw material, and through tert-butyloxycarbonyl protection reaction, coupling reaction, tert-butyloxycarbonyl deprotection reaction and recrystallization, a high-purity amino acid benzyl ester hydrochloride is prepared. The preparation method provided by the present invention does not need to use toxic organic solvents, nor does it need to use benzyl alcohol and catalysts, saving synthesis costs, and a large amount of waste water will not be produced during the synthesis process, simplifying the operation process, and the synthesis route is safer and more environmentally friendly. The present invention is used to effectively solve the existing method of synthesizing amino acid benzyl ester hydrochloride, which requires the use of toxic solvents, and the synthesis process will produce a large amount of waste water, easily introduce impurities, and cause the problem of low product purity, which provides a new idea for the synthesis of high-purity amino acid benzyl hydrochloride. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 This is the H NMR spectrum of the high-purity amino acid benzyl ester hydrochloride obtained in Example 1; Figure 2 This is the H NMR spectrum of the high-purity amino acid benzyl ester hydrochloride obtained in Example 2; Figure 3 This is the H NMR spectrum of the high-purity amino acid benzyl ester hydrochloride obtained in Example 3; Figure 4 This is the H NMR spectrum of the high-purity amino acid benzyl ester hydrochloride obtained in Example 4; Figure 5 This is the H NMR spectrum of the high-purity amino acid benzyl ester hydrochloride obtained in Example 5; Figure 6 This is the H NMR spectrum of the high-purity amino acid benzyl ester hydrochloride obtained in Example 6; Figure 7 This is the H NMR spectrum of the high-purity amino acid benzyl ester hydrochloride obtained in Example 7. DETAILED DESCRIPTION

[0028] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0029] Example 1 This embodiment provides a method for preparing high-purity amino acid benzyl ester hydrochloride, which specifically comprises the following steps: Step 1: Add 300 kg of glycine, 1000 kg of ethyl acetate, 500 kg of Boc anhydride and 300 kg of sodium hydroxide to a 3000 L reactor, perform tert-butyloxycarbonyl protection reaction at 60 ° C for 10 hours, cool to 10 ° C, centrifuge the reaction system at a speed of 1000 rpm, discard the solid salt, add water to the centrifuge for washing 3 times, add 100 kg of anhydrous sodium sulfate to dry for 22 hours, and then centrifuge at a speed of 1000 rpm for 5 minutes, collect the centrifuge to obtain Boc-amino acid; Step 2: Add 500 kg of benzyl bromide to the Boc-amino acid, and carry out coupling reaction at 5° C. for 12 hours. After the reaction is completed, add water to the reaction solution for washing 3 times, add anhydrous sodium sulfate to dry for 2 hours, and filter to obtain Boc-amino acid benzyl ester; Step 3, the Boc-amino acid benzyl ester was introduced with hydrogen chloride gas at a gas flow rate of 5 L / min for tert-butyloxycarbonyl deprotection reaction for 9 hours, and centrifuged at a speed of 1000 rpm for 5 minutes to obtain a solid filtrate; 600 kg of ethyl acetate was added to the solid filtrate, recrystallized at 28 ° C for 14 hours, centrifuged at a speed of 500 rpm for 5 minutes, the liquid was discarded, and dried at 60 ° C for 8 hours to obtain 632 kg of high-purity amino acid benzyl ester hydrochloride, and the yield was calculated to be 81%; after testing, the purity was 99.7%.

[0030] Example 2 This embodiment provides a method for preparing high-purity amino acid benzyl ester hydrochloride, which specifically comprises the following steps: Step 1: Add 300 kg of leucine, 1000 kg of isopropyl acetate, 480 kg of Boc anhydride and 300 kg of sodium hydroxide to a 3000 L reactor, perform tert-butyloxycarbonyl protection reaction at 60 ° C for 10 hours, cool to 10 ° C, centrifuge the reaction system at a speed of 1000 rpm, discard the solid salt, add water to the centrifuge for washing 3 times, add 70 kg of anhydrous sodium sulfate to dry for 2 hours, and then centrifuge at a speed of 1000 rpm for 5 minutes, collect the centrifuge to obtain Boc-amino acid; Step 2: Add 450 kg of benzyl chloride to the Boc-amino acid, and carry out coupling reaction at 15° C. for 15 hours. After the reaction is completed, add water to the reaction solution for washing 3 times, add anhydrous sodium sulfate to dry for 2 hours, and filter to obtain Boc-amino acid benzyl ester; Step 3, the Boc-amino acid benzyl ester was introduced with hydrogen chloride gas at a gas flow rate of 10 L / min for tert-butyloxycarbonyl deprotection reaction for 8 hours, and centrifuged at a speed of 1000 rpm for 5 minutes to obtain a solid filtrate; 700 kg of isopropyl acetate was added to the solid filtrate, recrystallized at 25 ° C for 16 hours, centrifuged at a speed of 500 rpm for 5 minutes, the liquid was discarded, and dried at 55 ° C for 9 hours to obtain 510 kg of high-purity amino acid benzyl ester hydrochloride, and the yield was calculated to be 87%; after testing, the purity was 99.6%.

[0031] Example 3 This embodiment provides a method for preparing high-purity amino acid benzyl ester hydrochloride, which specifically comprises the following steps: Step 1: Add 300 kg of proline, 1000 kg of tert-butyl acetate, 460 kg of Boc anhydride and 300 kg of sodium hydroxide to a 3000 L reactor, perform tert-butyloxycarbonyl protection reaction at 60 ° C for 10 hours, cool to 10 ° C, centrifuge the reaction system at a speed of 1000 rpm, discard the solid salt, add water to the centrifuge for washing 3 times, add 100 kg of anhydrous sodium sulfate to dry for 2 hours, and then centrifuge at a speed of 1000 rpm for 5 minutes, collect the centrifuge to obtain Boc-amino acid; Step 2: Add 430 kg of benzyl bromide to the Boc-amino acid, and carry out coupling reaction at 15° C. for 18 hours. After the reaction is completed, add water to the reaction solution for washing 3 times, add anhydrous sodium sulfate to dry for 2 hours, and filter to obtain Boc-amino acid benzyl ester; Step 3, the Boc-amino acid benzyl ester was introduced with hydrogen chloride gas at a gas flow rate of 10 L / min for tert-butyloxycarbonyl deprotection reaction for 8 hours, and centrifuged at a speed of 1000 rpm for 5 minutes to obtain a solid filtrate; 800 kg of tert-butyl acetate was added to the solid filtrate, recrystallized at 26 ° C for 14 hours, centrifuged at a speed of 500 rpm for 5 minutes, the liquid was discarded, and dried at 60 ° C for 8 hours to obtain 490 kg of high-purity amino acid benzyl ester hydrochloride, and the yield was calculated to be 78%; after testing, the purity was 99.6%.

[0032] Example 4 This embodiment provides a method for preparing high-purity amino acid benzyl ester hydrochloride, which specifically comprises the following steps: Step 1: Add 300 kg of threonine, 1000 kg of methyl acetate, 466 kg of Boc anhydride and 300 kg of potassium hydroxide to a 3000 L reactor, perform tert-butyloxycarbonyl protection reaction at 60 ° C for 10 hours, cool to 10 ° C, centrifuge the reaction system at a speed of 1000 rpm, discard the solid salt, add water to the centrifuge for washing 3 times, add 100 kg of anhydrous sodium sulfate to dry for 2 hours, and then centrifuge at a speed of 1000 rpm for 5 minutes, collect the centrifuge to obtain Boc-amino acid; Step 2: Add 480 kg of benzyl bromide to the Boc-amino acid, and carry out coupling reaction at 15° C. for 16 hours. After the reaction is completed, add water to the reaction solution for washing 3 times, add anhydrous sodium sulfate to dry for 2 hours, and filter to obtain Boc-amino acid benzyl ester; Step 3, the Boc-amino acid benzyl ester was introduced with hydrogen chloride gas at a gas flow rate of 10 L / min for tert-butyloxycarbonyl deprotection reaction for 8 hours, and centrifuged at a speed of 1000 rpm for 5 minutes to obtain a solid filtrate; 600 kg of methyl acetate was added to the solid filtrate, recrystallized at 30 ° C for 12 hours, centrifuged at a speed of 500 rpm for 5 minutes, the liquid was discarded, and dried at 55 ° C for 8 hours to obtain 502 kg of high-purity amino acid benzyl ester hydrochloride, and the yield was calculated to be 83%; after testing, the purity was 99.7%.

[0033] Example 5 This embodiment provides a method for preparing high-purity amino acid benzyl ester hydrochloride, which specifically comprises the following steps: Step 1: Add 300 kg of serine, 1000 kg of methyl acetate, 476 kg of Boc anhydride and 300 kg of sodium hydroxide to a 3000 L reactor, perform tert-butyloxycarbonyl protection reaction at 60 ° C for 10 hours, cool to 10 ° C, centrifuge the reaction system at a speed of 1000 rpm, discard the solid salt, add water to the centrifuge for washing 3 times, add 75 kg of anhydrous sodium sulfate to dry for 2 hours, and then centrifuge at a speed of 1000 rpm for 5 minutes, collect the centrifuge to obtain Boc-amino acid; Step 2: Add 520 kg of benzyl bromide to the Boc-amino acid, and carry out coupling reaction at 10° C. for 15 hours. After the reaction is completed, add water to the reaction solution for washing 3 times, add anhydrous sodium sulfate to dry for 2 hours, and filter to obtain Boc-amino acid benzyl ester; Step 3, the Boc-amino acid benzyl ester was introduced with hydrogen chloride gas at a gas flow rate of 10 L / min for tert-butyloxycarbonyl deprotection reaction for 8 hours, and centrifuged at a speed of 1000 rpm for 5 minutes to obtain a solid filtrate; 700 kg of methyl acetate was added to the solid filtrate, recrystallized at 25 ° C for 16 hours, centrifuged at a speed of 500 rpm for 5 minutes, the liquid was discarded, and dried at 55 ° C for 8 hours to obtain 554 kg of high-purity amino acid benzyl ester hydrochloride, and the yield was calculated to be 84%; after testing, the purity was 99.7%.

[0034] Example 6 This embodiment provides a method for preparing high-purity amino acid benzyl ester hydrochloride, which specifically comprises the following steps: Step 1: Add 300 kg of phenylalanine, 1000 kg of isopropyl acetate, 376 kg of Boc anhydride and 300 kg of potassium hydroxide to a 3000 L reactor, perform tert-butyloxycarbonyl protection reaction at 60 ° C for 10 hours, cool to 10 ° C, centrifuge the reaction system at a speed of 1000 rpm, discard the solid salt, add water to the centrifuge for washing 3 times, add 100 kg of anhydrous sodium sulfate to dry for 2 hours, and then centrifuge at a speed of 1000 rpm for 5 minutes, collect the centrifuge to obtain Boc-amino acid; Step 2: Add 320 kg of benzyl bromide to the Boc-amino acid, and carry out coupling reaction at 12° C. for 15 hours. After the reaction is completed, add water to the reaction solution for washing 3 times, add anhydrous sodium sulfate to dry for 2 hours, and filter to obtain Boc-amino acid benzyl ester; Step 3, the Boc-amino acid benzyl ester was subjected to a tert-butyloxycarbonyl deprotection reaction at a gas flow rate of 10 L / min by introducing hydrogen chloride gas for 9 hours, and the mixture was centrifuged at a speed of 1000 rpm for 5 minutes to obtain a solid filtrate; 700 kg of tert-butyl acetate was added to the solid filtrate, and the mixture was recrystallized at 28 ° C for 14 hours, centrifuged at a speed of 500 rpm for 5 minutes, the liquid was discarded, and the mixture was dried at 60 ° C for 9 hours to obtain 439 kg of high-purity amino acid benzyl ester hydrochloride, and the yield was calculated to be 83%; the purity was tested to be 99.8%.

[0035] Example 7 This embodiment provides a method for preparing high-purity amino acid benzyl ester hydrochloride, which specifically comprises the following steps: Step 1: Add 300 kg of 2-aminoisobutyric acid, 1000 kg of methyl acetate, 416 kg of Boc anhydride and 300 kg of sodium hydroxide to a 3000 L reactor, perform tert-butyloxycarbonyl protection reaction at 60 ° C for 10 hours, cool to 10 ° C, centrifuge the reaction system at a speed of 1000 rpm, discard the solid salt, add water to the centrifuge for washing 3 times, add 100 kg of anhydrous sodium sulfate to dry for 2 hours, and then centrifuge at a speed of 1000 rpm for 6 minutes, collect the centrifuge to obtain Boc-2 amino acid; Step 2: Add 480 kg of benzyl bromide to the Boc-amino acid, and carry out coupling reaction at 10° C. for 12 hours. After the reaction is completed, add water to the reaction solution for washing 3 times, add anhydrous sodium sulfate to dry for 2 hours, and filter to obtain Boc-amino acid benzyl ester; Step 3, the Boc-amino acid benzyl ester was introduced with hydrogen chloride gas at a gas flow rate of 10 L / min for tert-butyloxycarbonyl deprotection reaction for 8 hours, and centrifuged at a speed of 1000 rpm for 5 minutes to obtain a solid filtrate; 700 kg of tert-butyl acetate was added to the solid filtrate, recrystallized at 28 ° C for 14 hours, centrifuged at a speed of 500 rpm for 5 minutes, the liquid was discarded, and dried at 60 ° C for 8 hours to obtain 564 kg of high-purity amino acid benzyl ester hydrochloride, and the yield was calculated to be 85%; after testing, the purity was 99.6%.

[0036] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modification, equivalent substitution or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing high-purity amino acid benzyl ester hydrochloride, characterized in that: The steps include: Step 1: dissolving the amino acid in an organic ester solvent, adding Boc anhydride and a strong base, and performing a tert-butyloxycarbonyl protection reaction to obtain a Boc-amino acid; Step 2, adding benzyl halide to the Boc-amino acid for coupling reaction to obtain Boc-amino acid benzyl ester; Step 3: performing a tert-butyloxycarbonyl deprotection reaction on the Boc-amino acid benzyl ester to obtain high-purity amino acid benzyl ester hydrochloride.

2. The method for preparing high-purity amino acid benzyl ester hydrochloride according to claim 1, wherein: The steps include: In step 1, the amino acid is dissolved in an organic ester solvent, Boc anhydride and a strong base are added, and a tert-butyloxycarbonyl protection reaction is carried out at 50-70° C., the temperature is lowered to 8-12° C., the solid-liquid separation is performed, the washing is performed, and the drying is performed to obtain a Boc-amino acid; Step 2, adding benzyl halide to the Boc-amino acid, carrying out coupling reaction at 0-20° C., washing, and drying to obtain Boc-amino acid benzyl ester; Step 3: subjecting the Boc-amino acid benzyl ester to tert-butyloxycarbonyl deprotection reaction, solid-liquid separation, and recrystallization of the solid filtrate to obtain high-purity amino acid benzyl ester hydrochloride.

3. The method for preparing high-purity amino acid benzyl ester hydrochloride according to claim 1 or 2, characterized in that: In step 1, the amino acid includes any one of glycine, proline, leucine, phenylalanine, threonine, serine or 2-aminoisobutyric acid; and / or In step 1, the strong base is sodium hydroxide or potassium hydroxide; and / or In step 1, the organic ester solvent is any one of ethyl acetate, isopropyl acetate, tert-butyl acetate or methyl acetate.

4. The method for preparing high-purity amino acid benzyl ester hydrochloride according to claim 1 or 2, characterized in that: In step 1, the mass ratio of the amino acid to the organic ester solvent is 1:3-1:4; and / or In step 1, the molar ratio of the amino acid to the Boc anhydride is 0.6:1-1.8:1; and / or In step 1, the mass ratio of the amino acid to the strong base is 1:1-1:1.

1.

5. The method for preparing high-purity amino acid benzyl ester hydrochloride according to claim 2, characterized in that: In step 1, the tert-butyloxycarbonyl protection reaction time is 9h-12h; and / or In step 2, the coupling reaction time is 6h-24h.

6. The method for preparing high-purity amino acid benzyl ester hydrochloride according to claim 1 or 2, characterized in that: In step 2, the molar ratio of the Boc-amino acid to the benzyl halide is 1:1-1:

2.

7. The method for preparing high-purity amino acid benzyl ester hydrochloride according to claim 1 or 2, characterized in that: In step 3, the specific operation of the tert-butyloxycarbonyl deprotection reaction includes the following steps: introducing hydrogen chloride gas into the Boc-amino acid benzyl ester to carry out the tert-butyloxycarbonyl deprotection reaction.

8. The method for preparing high-purity amino acid benzyl ester hydrochloride according to claim 7, characterized in that: In step 3, the amount of hydrogen chloride gas introduced is 1 L / min-10 L / min; and / or In step 3, the introduction time of the hydrogen chloride gas is 6h-12h.

9. The method for preparing high-purity amino acid benzyl ester hydrochloride according to claim 2, characterized in that: In step 3, the recrystallization temperature is 20°C-30°C, and the recrystallization time is 12h-18h.

10. The method for preparing high-purity amino acid benzyl ester hydrochloride according to claim 2 or 9, characterized in that: The recrystallization solvent is any one of ethyl acetate, isopropyl acetate, tert-butyl acetate or methyl acetate.

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