(S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol and preparation method thereof

Abstract

The invention relates to (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol and a preparation method thereof, and belongs to the technical field of organic synthesis. The preparation method comprises the following steps: adding a 4-(1-hydroxy-2-aminoethyl) phenol hydrochloride substrate into an alcohol solvent, and adding alkali and R-(-)-camphor-10-sulfonic acid for reaction to obtain a product A; adding the product A into a solvent, dropwise adding nitric acid with the mass fraction of 65-68%, and reacting at normal temperature to obtain a product B; the product B is added into a solvent, alkali and di-tert-butyl dicarbonate ester are added for a reaction, and (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol is obtained. The preparation method disclosed by the invention is free of chiral resolution, mild in condition, low in equipment requirement, less in side reaction, accurate in material proportion in each step, suitable for large-scale production and capable of stably and efficiently synthesizing a target compound.

Description

Technical Field

[0001] The invention belongs to the technical field of polymer materials and relates to (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol and a preparation method thereof. Background Art

[0002] (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol is a key chiral drug intermediate that plays an important role in drug synthesis. For example, it serves as a core fragment for the synthesis of anti-tumor drugs, anti-inflammatory drugs, or neurological drugs. Its chiral purity directly affects the activity and safety of the final drug.

[0003] In the prior art, patents WO2022 / 207699 and WO2023 / 170247 require separation using a chiral chromatographic column to obtain the target chiral product. This method requires expensive chiral column materials and complex operations, significantly increasing production costs and making large-scale industrial production difficult. Traditional nitration reactions require the use of strong acids such as concentrated sulfuric acid as catalysts and are carried out at high temperatures. Strong acid environments can easily lead to racemization of chiral centers, reducing the optical purity of the product. High temperatures can trigger side reactions such as polynitration and oxidation, resulting in reduced overall yields and hindering industrialization.

[0004] Therefore, it is urgent to develop a method for preparing (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol. Summary of the Invention

[0005] In view of the shortcomings of the prior art, the present invention aims to provide a (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol and a preparation method thereof, which have the characteristics of not requiring chiral chromatographic column separation, mild conditions, and suitability for scale-up.

[0006] The purpose of the present invention can be achieved through the following technical solutions: A (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol, wherein the structural formula of the (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol is .

[0007] A method for preparing (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol, wherein the specific steps of the preparation method are as follows: S1, salt formation and resolution: adding the substrate to an alcohol solvent, adding an inorganic base, and then adding R-(-)-camphor-10-sulfonic acid to carry out a salt formation reaction to obtain product A; S2, nitration: adding product A to a solvent, adding nitric acid dropwise to carry out nitration reaction to obtain product B; S3, Boc protection: adding product B to a solvent, adding an inorganic base and di-tert-butyl dicarbonate to react to obtain the (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol; The substrate in S1 is 4-(1-hydroxy-2-aminoethyl)phenol hydrochloride.

[0008] As a preferred technical solution of the present invention, the alcohol solvent in S1 is one of methanol, ethanol, isopropanol or tert-butanol; the inorganic base is one of sodium carbonate, potassium carbonate, cesium carbonate, lithium hydroxide, sodium hydroxide or potassium hydroxide.

[0009] As a preferred technical solution of the present invention, the weight ratio of the solvent to the substrate in S1 is (5-25):1, the molar ratio of the inorganic base to the substrate is (0.95-1.05):1, and the molar ratio of R-(-)-camphor-10-sulfonic acid to the substrate is 0.95:1.05.

[0010] As a preferred technical solution of the present invention, the solvent in S2 is one or more of acetic acid, propionic acid and water; and the mass fraction of nitric acid is 65-68%.

[0011] As a preferred technical solution of the present invention, the weight ratio of the solvent to the substrate in S2 is (4-15):1; the molar ratio of nitric acid to the substrate is (1.0-1.5):1.

[0012] As a preferred technical solution of the present invention, the solvent in S3 is one or more of methanol, ethanol, isopropanol, tetrahydrofuran, ethyl acetate, dichloromethane and water; the inorganic base is one of sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate, lithium hydroxide, sodium hydroxide or potassium hydroxide.

[0013] As a preferred technical solution of the present invention, the weight ratio of the solvent to the substrate in S3 is (4-15):1; the molar ratio of di-tert-butyl dicarbonate to the substrate is (1-2):1; and the molar ratio of the inorganic base to the substrate is (2-4):1.

[0014] Beneficial effects of the present invention: (1) The preparation method provided by the present invention uses R-(-)-camphor-10-sulfonic acid for chiral splitting during the synthesis process to obtain 4-(1-hydroxy-2-aminoethyl)phenol R-(-)-camphor-10-sulfonate with high chiral purity, thereby avoiding the subsequent complex chiral splitting step, greatly simplifying the synthesis process, improving the utilization rate of raw materials, and reducing production costs.

[0015] (2) Each reaction step in the entire preparation process is carried out under relatively mild conditions, which places low demands on equipment and does not require special high-temperature and high-pressure equipment, thus reducing equipment investment costs. At the same time, mild conditions are also conducive to reducing the occurrence of side reactions and improving the purity and yield of the product. In addition, mild conditions can better protect the structural stability of the substrate or intermediate, ensuring the smooth progress of the reaction. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] To facilitate understanding by those skilled in the art, the present invention is further described below with reference to the accompanying drawings.

[0017] Figure 1 The synthetic route of the present invention is shown in FIG. DETAILED DESCRIPTION

[0018] In order to further illustrate the technical means and effects adopted by the present invention to achieve the predetermined purpose of the invention, the specific implementation methods, structures, features and effects of the present invention are described in detail below in conjunction with the accompanying drawings and preferred embodiments.

[0019] In the Examples and Comparative Examples of the present invention: 4-(1-Hydroxy-2-aminoethyl)phenol hydrochloride: CAS: 770-05-8, purchased from Wanghua Yanxuan (Shanghai) Chemical Technology Co., Ltd., industrial grade; R-(-)-Camphor-10-sulfonic acid: CAS: 35963-20-3, purchased from Beijing Bai Nian Nuan Technology Co., Ltd., industrial grade.

[0020] Example 1 S1: Add 3550.0 kg of ethanol and 150.0 kg of 4-(1-hydroxy-2-aminoethyl)phenol hydrochloride, control the temperature at 25°C under nitrogen protection, and add 31.6 kg of sodium hydroxide in batches; after the addition is completed, stir at room temperature for 2-4 hours.

[0021] Filter, control the temperature at 45°C, concentrate the filtrate to 1550.0 L, control the temperature at 25°C, add R-(-)-camphor-10-sulfonic acid in batches, stir at 25°C for 12.5 hours, and filter.

[0022] Add the filter cake and 1065.0 kg of ethanol to the reactor, control the temperature at 60°C, and stir to dissolve. Cool to 40°C, add seed crystals, and then control the temperature at 40°C and stir for 2 hours. Then, cool to 25°C at a gradient rate of 7.5°C / hour, and then stir at 25°C for 9 hours. Filter.

[0023] Add the filter cake and 475.0 kg of ethanol to the reactor, control the temperature at 67.5°C, and stir to dissolve. Then cool to 55°C, add seed crystals, and continue stirring at 55°C for 2 hours. Then, cool to 25°C at a gradient rate of 7.5°C / hour, and then stir at 25°C for 9 hours. Filter.

[0024] The filter cake and 295.0 kg of ethanol were added to a reactor, stirred at 72.5°C until dissolved, then cooled to 58°C. Seed crystals were added, and the temperature was then controlled at 55°C and stirred for 2 hours. The temperature was then gradually decreased at 7.5°C / hour to 25°C, followed by stirring at 25°C for 9 hours. The mixture was filtered. The filter cake was dried to yield 26.6 kg of 4-(1-hydroxy-2-aminoethyl)phenol R-(-)-camphor-10-sulfonate as a white solid with a chemical purity of 100.0%, a chiral purity of 100.0%, and a yield of 8.7%.

[0025] 1 H-NMR (400 MHz, DMSO): δ = 9.42 (1H, s), δ = 7.80 (3H, brs), δ =7.18 (2H, d, J = 8.4 Hz), δ = 6.76 (2H, d, J = 8.8 Hz), δ = 5.87 (1H, d, J =2.8 Hz), δ = 4.66 (1H, m), δ = 2.95 (1H, dd, J = 12.8, 2.4 Hz), δ = 2.87 (1H,d, J = 14.4 Hz), δ = 2.81 (1H, dd, J = 12.8, 10.0 Hz), δ = 2.70 (1H, m), δ =2.37 (1H, d, J = 14.8 Hz), δ = 2.24 (1H, dt, J = 18.0, 4.0 Hz), δ = 1.94 (1H,t, J = 4.4 Hz), δ = 1.87 (1H, m), δ = 1.80 (1H, d, J = 18.0 Hz), δ = 1.28(2H, m), δ = 1.06 (3H, s), δ = 0.75 (3H, s).

[0026] S2: Add 230.0 kg of acetic acid and 22.0 kg of 4-(1-hydroxy-2-aminoethyl)phenol R-(-)-camphor-10-sulfonate. Maintain the temperature at 25°C, then add 6.6 kg of 66.5% concentrated nitric acid dropwise. Continue the reaction for 1.5 hours, then filter. Combine the filter cake and 70.0 kg of ethanol, stir at 25°C for 4 hours. Filter and dry the filter cake to yield 17.6 kg of 4-[(1S)-2-amino-1-hydroxyethyl]-2-nitrophenol R-(-)-camphor-10-sulfonate with a chemical purity of 98.2%, a chiral purity of 100.0%, and a yield of 71.7%.

[0027] 1 H-NMR (400 MHz, DMSO): δ = 11.02 (1H, brs), δ = 7.90 (4H, brs), δ =7.56 (1H, dd, J = 8.4, 2.0 Hz), δ = 7.16 (1H, d, J = 8.4 Hz), δ = 6.15 (1H,brs), δ = 4.82 (1H, dd, J = 9.2, 3.2 Hz), δ = 3.06 (1H, m), δ = 2.91 (1H, d,J = 14.8 Hz), δ = 2.83 (1H, m), δ = 2.66 (1H, m), δ = 2.42 (1H, d, J = 14.8Hz), δ = 2.25 (1H, dt, J = 18.0, 4.0 Hz), δ = 1.95 (1H, t, J = 4.4 Hz), δ =1.87 (1H, m), δ = 1.80 (1H, d, J = 18.0 Hz), δ = 1.29 (2H, m), δ = 1.05 (3H,s), δ = 0.75 (3H,s).

[0028] S3: Add 105.0 kg of ethanol and 17.6 kg of 4-[(1S)-2-amino-1-hydroxyethyl]-2-nitrophenol R-(-)-camphor-10-sulfonate, control the temperature at 25°C, add 48.0 kg of saturated aqueous sodium bicarbonate solution dropwise, stir for 13.5 hours, filter, add the filter cake and 42.0 kg of ethanol to the reactor, control the temperature at 25°C, stir for 4 hours, and filter. The filter cake and 91.0 kg of process water were added to the reactor, and 12.0 kg of sodium bicarbonate and 16.2 kg of di-tert-butyl dicarbonate were added respectively. The temperature was controlled at 30°C and stirred for 17.5 hours. The mixture was extracted three times with 32.0 kg of ethyl acetate, and the ethyl acetate phases were combined and dried over anhydrous sodium sulfate. The dried organic phase was concentrated to 30 liters, and 115.0 kg of petroleum ether was added dropwise. The temperature was controlled at 25°C and stirred for 7 hours. The mixture was filtered and the filter cake was dried to obtain 6.8 kg of (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol with a chemical purity of 100.0%, a chiral purity of 99.6%, and a yield of 55.7%.

[0029] 1 H-NMR (400 MHz, CDCl3): δ = 10.54 (1H, brs), δ = 8.12 (1H, d, J =2.0 Hz), δ = 7.60 (1H, dd, J = 8.8, 2.0 Hz), δ = 7.15 (1H, d, J = 8.8 Hz), δ= 4.94 (1H, brs), δ = 4.85 (1H, d, J = 5.2 Hz), δ = 3.65 (1H, brs), δ = 3.47(1H, m), δ = 3.24 (1H, m), δ = 1.45 (9H, s).

[0030] Example 2 S1: Add 3550.0 kg of ethanol and 150.0 kg of 4-(1-hydroxy-2-aminoethyl)phenol hydrochloride, control the temperature at 20°C under nitrogen protection, and add 31.6 kg of sodium hydroxide in batches; after the addition is complete, stir at room temperature for 2 hours.

[0031] Filter, control the temperature at 40°C, concentrate the filtrate to 1500.0 L, control the temperature at 20°C, add R-(-)-camphor-10-sulfonic acid in batches, stir at 20°C for 10 hours, and filter.

[0032] Add the filter cake and 1065.0 kg of ethanol to a reactor, control the temperature at 55°C, and stir to dissolve. Cool to 40°C, add seed crystals, and then control the temperature at 35°C and stir for 1 hour. Then, cool to 20°C at a gradient rate of 5°C / hour, and then stir at 20°C for 8 hours. Filter.

[0033] Add the filter cake and 475.0 kg of ethanol to the reactor, control the temperature at 65°C, and stir to dissolve. Cool to 55°C, add seed crystals, and then control the temperature at 50°C and stir for 1 hour. Then, cool to 20°C at a rate of 5°C / hour, and then stir at 20°C for 8 hours. Filter.

[0034] The filter cake and 295.0 kg of ethanol were added to a reactor, stirred at 70°C until dissolved, then cooled to 58°C. Seed crystals were added, and the temperature was then controlled at 50°C and stirred for 1 hour. The temperature was then gradually decreased to 20°C at a rate of 5°C / hour, followed by stirring at 20°C for 8 hours. The mixture was filtered. The filter cake was dried to yield 26.6 kg of 4-(1-hydroxy-2-aminoethyl)phenol R-(-)-camphor-10-sulfonate as a white solid with a chemical purity of 100.0%, a chiral purity of 100.0%, and a yield of 8.5%.

[0035] S2: Add 230.0 kg of acetic acid and 22.0 kg of 4-(1-hydroxy-2-aminoethyl)phenol R-(-)-camphor-10-sulfonate. Maintain the temperature at 20°C, then add 6.6 kg of 65% concentrated nitric acid dropwise. Continue the reaction for 1 hour, then filter. Stir the filter cake and 70.0 kg of ethanol at 20°C for 3 hours. Filter and dry the filter cake to yield 17.6 kg of 4-[(1S)-2-amino-1-hydroxyethyl]-2-nitrophenol R-(-)-camphor-10-sulfonate with a chemical purity of 98.0%, a chiral purity of 100.0%, and a yield of 70.4%.

[0036] S3: Add 105.0 kg of ethanol and 17.6 kg of 4-[(1S)-2-amino-1-hydroxyethyl]-2-nitrophenol R-(-)-camphor-10-sulfonate, control the temperature at 20°C, add 48.0 kg of saturated sodium bicarbonate aqueous solution dropwise, stir for 12 hours, filter, add the filter cake and 42.0 kg of ethanol to the reactor, control the temperature at 20°C, stir for 3 hours, and filter. The filter cake and 91.0 kg of process water were added to the reactor, and 12.0 kg of sodium bicarbonate and 16.2 kg of di-tert-butyl dicarbonate were added respectively. The temperature was controlled at 25°C and stirred for 15 hours. The mixture was extracted three times with 32.0 kg of ethyl acetate, and the ethyl acetate phases were combined and dried over anhydrous sodium sulfate. The dried organic phase was concentrated to 20 liters, and 115.0 kg of petroleum ether was added dropwise. The temperature was controlled at 20°C and stirred for 6 hours. The mixture was filtered and the filter cake was dried to obtain 6.8 kg of (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol with a chemical purity of 100.0%, a chiral purity of 99.4%, and a yield of 55.2%.

[0037] Example 3 S1: Add 3550.0 kg of ethanol and 150.0 kg of 4-(1-hydroxy-2-aminoethyl)phenol hydrochloride, control the temperature at 30°C under nitrogen protection, and add 31.6 kg of sodium hydroxide in batches; after the addition is complete, stir at room temperature for 4 hours.

[0038] Filter, control the temperature at 50°C, concentrate the filtrate to 1600.0 L, control the temperature at 30°C, add R-(-)-camphor-10-sulfonic acid in batches, stir at 30°C for 15 hours, and filter.

[0039] Add the filter cake and 1065.0 kg of ethanol to a reactor, control the temperature at 65°C, and stir to dissolve. Cool to 40°C, add seed crystals, and then control the temperature at 45°C and stir for 3 hours. Then, cool to 30°C at a rate of 10°C / hour, and then stir at 30°C for 10 hours. Filter.

[0040] Add the filter cake and 475.0 kg of ethanol to the reactor, control the temperature at 70°C, and stir to dissolve. Cool to 55°C, add seed crystals, and then control the temperature at 60°C and stir for 3 hours. Then, cool to 30°C at a rate of 10°C / hour, and then stir at 30°C for 10 hours. Filter.

[0041] The filter cake and 295.0 kg of ethanol were added to a reactor, stirred at 75°C until dissolved, then cooled to 58°C. Seed crystals were added, and the temperature was then controlled at 60°C and stirred for 3 hours. The temperature was then gradually decreased at 10°C / hour to 30°C, followed by stirring at 30°C for 10 hours. The mixture was filtered. The filter cake was dried to yield 26.6 kg of 4-(1-hydroxy-2-aminoethyl)phenol R-(-)-camphor-10-sulfonate as a white solid with a chemical purity of 100.0%, a chiral purity of 100.0%, and a yield of 8.6%.

[0042] S2: Add 230.0 kg of acetic acid and 22.0 kg of 4-(1-hydroxy-2-aminoethyl)phenol R-(-)-camphor-10-sulfonate. Maintain the temperature at 30°C, then add 6.6 kg of 68% concentrated nitric acid dropwise. Continue the reaction for 2 hours and filter. Stir the filter cake and 70.0 kg of ethanol at 30°C for 5 hours. Filter and dry the filter cake to yield 17.6 kg of 4-[(1S)-2-amino-1-hydroxyethyl]-2-nitrophenol R-(-)-camphor-10-sulfonate with a chemical purity of 97.9%, a chiral purity of 100.0%, and a yield of 71.2%.

[0043] S3: Add 105.0 kg of ethanol and 17.6 kg of 4-[(1S)-2-amino-1-hydroxyethyl]-2-nitrophenol R-(-)-camphor-10-sulfonate, control the temperature at 30°C, add 48.0 kg of saturated sodium bicarbonate aqueous solution dropwise, stir for 15 hours, filter, add the filter cake and 42.0 kg of ethanol to the reactor, control the temperature at 30°C, stir for 5 hours, and filter. The filter cake and 91.0 kg of process water were added to the reactor, and 12.0 kg of sodium bicarbonate and 16.2 kg of di-tert-butyl dicarbonate were added respectively. The temperature was controlled at 35°C and stirred for 20 hours. The mixture was extracted three times with 32.0 kg of ethyl acetate, and the ethyl acetate phases were combined and dried over anhydrous sodium sulfate. The dried organic phase was concentrated to 40 liters, and 115.0 kg of petroleum ether was added dropwise. The temperature was controlled at 30°C and stirred for 8 hours. The mixture was filtered and the filter cake was dried to obtain 6.8 kg of (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol with a chemical purity of 100.0%, a chiral purity of 99.2%, and a yield of 55.0%.

[0044] Comparative Example 1 D-(-)-tartaric acid was used in step S1, and the remaining steps were the same as in Example 1. No obvious resolution effect was observed.

[0045] Comparative Example 2 In step S2, 75% concentrated nitric acid was added, and the remaining steps were the same as in Example 1.

[0046] The final (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol obtained had a chemical purity of 97.2%, a chiral purity of 98.3%, and a yield of 51.2%.

[0047] Comparative Example 3 In step S2, 50% concentrated nitric acid was added, and the remaining steps were the same as in Example 1.

[0048] The final (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol obtained had a chemical purity of 97.9%, a chiral purity of 98.9%, and a yield of 48.8%.

[0049] Comparative Example 4 In step S3, dichloromethane was used instead of ethyl acetate for extraction, and the remaining steps were the same as those in Example 1.

[0050] The final (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol obtained had a chemical purity of 97.6%, a chiral purity of 99.0%, and a yield of 52.6%.

[0051] The above description is merely a preferred embodiment of the present invention and does not constitute any form of limitation to the present invention. Although the present invention has been disclosed as a preferred embodiment as above, it is not intended to limit the present invention. Any person skilled in the art can make some changes or modifications to equivalent embodiments using the technical contents disclosed above without departing from the scope of the technical solution of the present invention. However, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. A method for preparing (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol, characterized in that: The specific steps of the preparation method are as follows: S1, salt formation and resolution: adding the substrate to an alcohol solvent, adding an inorganic base, and then adding R-(-)-camphor-10-sulfonic acid to carry out a salt formation reaction to obtain product A; S2, nitration: adding product A to a solvent, adding nitric acid dropwise to carry out nitration reaction to obtain product B; S3, Boc protection: adding product B to a solvent, adding an inorganic base and di-tert-butyl dicarbonate to react to obtain the (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol; The substrate in S1 is 4-(1-hydroxy-2-aminoethyl)phenol hydrochloride.

2. The method for preparing (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol according to claim 1, wherein: The alcohol solvent in S1 is one of methanol, ethanol, isopropanol or tert-butanol; the inorganic base is one of sodium carbonate, potassium carbonate, cesium carbonate, lithium hydroxide, sodium hydroxide or potassium hydroxide.

3. The method for preparing (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol according to claim 1, wherein: In the S1, the weight ratio of the solvent to the substrate is (5-25):1, the molar ratio of the inorganic base to the substrate is (0.95-1.05):1, and the molar ratio of R-(-)-camphor-10-sulfonic acid to the substrate is 0.95:1.

05.

4. The method for preparing (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol according to claim 1, wherein: The solvent in S2 is one or more of acetic acid, propionic acid and water; the mass fraction of nitric acid is 65-68%.

5. The method for preparing (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol according to claim 1, wherein: The weight ratio of the solvent to the substrate in S2 is (4-15):1; the molar ratio of nitric acid to the substrate is (1.0-1.5):

1.

6. The method for preparing (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol according to claim 1, wherein: The solvent in S3 is one or more of methanol, ethanol, isopropanol, tetrahydrofuran, ethyl acetate, dichloromethane and water; the inorganic base is one of sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate, lithium hydroxide, sodium hydroxide or potassium hydroxide.

7. The method for preparing (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol according to claim 1, wherein: In the S3, the weight ratio of the solvent to the substrate is (4-15):1; the molar ratio of di-tert-butyl dicarbonate to the substrate is (1-2):1; and the molar ratio of the inorganic base to the substrate is (2-4):1.

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