(S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol and a process for its preparation

Abstract

This invention relates to (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol and its preparation method, belonging to the field of organic synthesis technology. The preparation method of this invention includes the following steps: adding 4-(1-hydroxy-2-aminoethyl)phenol hydrochloride substrate to an alcohol solvent, reacting with alkali and R-(-)-camphor-10-sulfonic acid to obtain product A; adding product A to a solvent, adding 65-68% nitric acid by mass, and reacting at room temperature to obtain product B; adding product B to a solvent, reacting with alkali and di-tert-butyl dicarbonate to obtain the (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol. The preparation method of this invention does not require chiral resolution, has mild conditions, low equipment requirements, few side reactions, and precise material ratios in each step, making it suitable for scale-up production and enabling stable and efficient synthesis of the target compound.

Description

Technical Field

[0001] This invention belongs to the field of polymer materials technology and relates to (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol and its preparation method. Background Technology

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

[0003] In existing technologies, patents WO2022 / 207699 and WO2023 / 170247 require chiral chromatographic column separation to obtain the target chiral product. This method requires expensive chiral column materials and complex operations, leading to a significant increase in production costs and making large-scale industrial production difficult. Traditional nitration reactions require strong acids such as concentrated sulfuric acid as catalysts and are carried out at high temperatures. The strong acid environment easily leads to racemization of the chiral center, reducing the optical purity of the product; high temperature conditions may also trigger side reactions such as polynitration and oxidation, resulting in a decrease in overall yield and hindering the industrialization process.

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

[0005] To address the shortcomings of existing technologies, the present invention aims to provide (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol and its preparation method, which features the advantages of not requiring chiral chromatographic column separation, mild conditions, and suitability for scale-up.

[0006] The objective of this invention can be achieved through the following technical solutions:

[0007] 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 as follows: .

[0008] A method for preparing (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol, wherein the specific steps of the preparation method are as follows.

[0009] S1. Salt formation and resolution: Add the substrate to an alcohol solvent, add an inorganic base, and then add R-(-)-camphor-10-sulfonic acid to carry out a salt formation reaction to obtain product A;

[0010] S2, Nitration: Product A is added to a solvent, and nitric acid is added dropwise to carry out the nitration reaction to obtain product B;

[0011] S3, Boc protection: Product B is added to a solvent, and an inorganic base and di-tert-butyl dicarbonate are added to react and obtain (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol.

[0012] The substrate in S1 is 4-(1-hydroxy-2-aminoethyl)phenol hydrochloride.

[0013] As a preferred embodiment 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.

[0014] As a preferred embodiment of the present invention, in S1, the weight ratio of solvent to substrate is (5~25):1, the molar ratio of inorganic base to substrate is (0.95~1.05):1, and the molar ratio of R-(-)-camphor-10-sulfonic acid to substrate is 0.95:1.05.

[0015] In a preferred embodiment of the present invention, the solvent in S2 is one or more of acetic acid, propionic acid and water; the mass fraction of nitric acid is 65-68%.

[0016] As a preferred embodiment of the present invention, the weight ratio of solvent to substrate in S2 is (4~15):1; the molar ratio of nitric acid to substrate is (1.0~1.5):1.

[0017] As a preferred embodiment 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.

[0018] In a preferred embodiment of the present invention, the weight ratio of solvent to substrate in S3 is (4~15):1; the molar ratio of ditert-butyl dicarbonate to substrate is (1~2):1; and the molar ratio of inorganic base to substrate is (2~4):1.

[0019] The beneficial effects of this invention are:

[0020] (1) The preparation method provided by the present invention uses R-(-)-camphor-10-sulfonic acid for chiral resolution during the synthesis process to obtain 4-(1-hydroxy-2-aminoethyl)phenol R-(-)-camphor-10-sulfonate with high chiral purity, which avoids the subsequent complex chiral resolution steps, greatly simplifies the synthesis process, improves the utilization rate of raw materials, and reduces production costs.

[0021] (2) All reaction steps in the entire preparation process are carried out under relatively mild conditions, which reduces the requirements for equipment and eliminates the need for special high-temperature and high-pressure resistant equipment, thus lowering equipment investment costs. At the same time, mild conditions also help reduce the occurrence of side reactions and improve 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. Attached Figure Description

[0022] To facilitate understanding by those skilled in the art, the present invention will be further described below with reference to the accompanying drawings.

[0023] Figure 1 This is a synthetic route diagram of the present invention. Detailed Implementation

[0024] To further illustrate the technical means and effects of the present invention in achieving its intended purpose, the following detailed description of the specific implementation methods, structures, features, and effects of the present invention, in conjunction with the accompanying drawings and preferred embodiments, is provided.

[0025] In the embodiments and comparative examples of this invention:

[0026] 4-(1-Hydroxy-2-aminoethyl)phenol hydrochloride: CAS: 770-05-8, purchased from NETChem.com (Shanghai) Chemical Technology Co., Ltd., industrial grade;

[0027] R-(-)-Camphor-10-sulfonic acid: CAS: 35963-20-3, purchased from Beijing Bainiannuan Technology Co., Ltd., industrial grade.

[0028] Example 1

[0029] S1:

[0030] Add 3550.0 kg of ethanol and 150.0 kg of 4-(1-hydroxy-2-aminoethyl)phenol hydrochloride, and under nitrogen protection, control the temperature at 25°C. Add 31.6 kg of sodium hydroxide in batches. After the addition is complete, stir at room temperature for 2-4 hours.

[0031] Filter, control the temperature at 45℃, concentrate the filtrate to 1550.0 L, control the temperature at 25℃, add R-(-)-camphor-10-sulfonic acid in batches, stir at 25℃ for 12.5 hours, and filter.

[0032] Add the filter cake and 1065.0 kg of ethanol to the reactor, maintain the temperature at 60°C while stirring to dissolve, cool to 40°C, add seed crystals, and then maintain the temperature at 40°C while stirring for 2 hours. Reduce the temperature to 25°C in a gradient of 7.5°C / hour, and then stir at 25°C for 9 hours. Filter.

[0033] Add the filter cake and 475.0 kg of ethanol to the reactor, maintain the temperature at 67.5℃ and stir until dissolved. Cool to 55℃, add seed crystals, and then maintain the temperature at 55℃ and stir for 2 hours. Reduce the temperature to 25℃ in a gradient of 7.5℃ / hour, and then stir at 25℃ for 9 hours. Filter.

[0034] The filter cake and 295.0 kg of ethanol were added to a reaction vessel, and the mixture was stirred and dissolved at 72.5℃. The temperature was then lowered to 58℃, seed crystals were added, and the mixture was stirred at 55℃ for 2 hours. The temperature was then gradually lowered to 25℃ at a rate of 7.5℃ / hour, and stirred at 25℃ for 9 hours. The mixture was then filtered. The filter cake was dried to obtain 26.6 kg of a white solid, 4-(1-hydroxy-2-aminoethyl)phenol R-(-)-camphor-10-sulfonate, with a chemical purity of 100.0% and a chiral purity of 100.0%, yielding 8.7%.

[0035] 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).

[0036] S2:

[0037] Add 230.0 kg of acetic acid and 22.0 kg of 4-(1-hydroxy-2-aminoethyl)phenol R-(-)-camphor-10-sulfonate, maintaining the temperature at 25°C. Add 6.6 kg of 66.5% concentrated nitric acid dropwise. After the addition is complete, continue the reaction for 1.5 hours, then filter. Mix the filter cake with 70.0 kg of ethanol, maintaining the temperature at 25°C, and stir for 4 hours. Filter, and dry the filter cake to obtain 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%.

[0038] 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).

[0039] S3:

[0040] 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℃, add 48.0 kg of saturated sodium bicarbonate aqueous solution dropwise, stir for 13.5 hours after the addition is complete, filter, add the filter cake and 42.0 kg of ethanol to the reaction vessel, control the temperature at 25℃, stir for 4 hours, and filter. 91.0 kg of filter cake and process water were added to a reactor, followed by 12.0 kg of sodium bicarbonate and 16.2 kg of di-tert-butyl dicarbonate. The temperature was controlled at 30°C, and the mixture was stirred for 17.5 hours. The mixture was extracted three times with 32.0 kg of ethyl acetate. The ethyl acetate phases were combined and dried with anhydrous sodium sulfate. The dried organic phase was concentrated to 30 L, and 115.0 kg of petroleum ether was added dropwise. The temperature was controlled at 25°C, and the mixture was 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%.

[0041] 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).

[0042] Example 2

[0043] S1:

[0044] Add 3550.0 kg of ethanol and 150.0 kg of 4-(1-hydroxy-2-aminoethyl)phenol hydrochloride, and under nitrogen protection, control the temperature at 20°C. Add 31.6 kg of sodium hydroxide in batches. After the addition is complete, stir at room temperature for 2 hours.

[0045] Filter, control the temperature at 40℃, concentrate the filtrate to 1500.0 L, control the temperature at 20℃, add R-(-)-camphor-10-sulfonic acid in batches, stir at 20℃ for 10 hours, and filter.

[0046] Add the filter cake and 1065.0 kg of ethanol to the reactor, maintain the temperature at 55°C while stirring to dissolve, cool to 40°C, add seed crystals, then maintain the temperature at 35°C and stir for 1 hour. Reduce the temperature to 20°C in a gradient of 5°C / hour, and then stir at 20°C for 8 hours. Filter.

[0047] Add the filter cake and 475.0 kg of ethanol to the reactor, maintain the temperature at 65°C while stirring to dissolve, cool to 55°C, add seed crystals, then maintain the temperature at 50°C and stir for 1 hour. Reduce the temperature to 20°C in a gradient of 5°C / hour, and then stir at 20°C for 8 hours. Filter.

[0048] The filter cake and 295.0 kg of ethanol were added to a reaction vessel, and the mixture was stirred and dissolved at 70°C. The temperature was then lowered to 58°C, seed crystals were added, and the mixture was stirred at 50°C for 1 hour. The temperature was then gradually lowered to 20°C at a rate of 5°C / hour, and then stirred at 20°C for 8 hours. The mixture was filtered. The filter cake was dried to obtain 26.6 kg of a white solid, 4-(1-hydroxy-2-aminoethyl)phenol R-(-)-camphor-10-sulfonate, with a chemical purity of 100.0% and a chiral purity of 100.0%, yielding 8.5%.

[0049] S2:

[0050] Add 230.0 kg of acetic acid and 22.0 kg of 4-(1-hydroxy-2-aminoethyl)phenol R-(-)-camphor-10-sulfonate, maintaining the temperature at 20°C. Add 6.6 kg of 65% concentrated nitric acid dropwise. After the addition is complete, continue the reaction for 1 hour, then filter. Mix the filter cake with 70.0 kg of ethanol, maintaining the temperature at 20°C, and stir for 3 hours. Filter, and dry the filter cake to obtain 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%.

[0051] S3:

[0052] 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℃, add 48.0 kg of saturated sodium bicarbonate aqueous solution dropwise, stir for 12 hours after the addition is complete, filter, add the filter cake and 42.0 kg of ethanol to the reaction vessel, control the temperature at 20℃, stir for 3 hours, and filter. 91.0 kg of filter cake and process water were added to a reactor, followed by 12.0 kg of sodium bicarbonate and 16.2 kg of di-tert-butyl dicarbonate. The mixture was stirred at 25°C for 15 hours. The mixture was extracted three times with 32.0 kg of ethyl acetate. The ethyl acetate phases were combined and dried with anhydrous sodium sulfate. The dried organic phase was concentrated to 20 L, and 115.0 kg of petroleum ether was added dropwise. The mixture was stirred at 20°C for 6 hours, 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%.

[0053] Example 3

[0054] S1:

[0055] Add 3550.0 kg of ethanol and 150.0 kg of 4-(1-hydroxy-2-aminoethyl)phenol hydrochloride, and under nitrogen protection, control the temperature at 30°C. Add 31.6 kg of sodium hydroxide in batches. After the addition is complete, stir at room temperature for 4 hours.

[0056] Filter, control the temperature at 50℃, concentrate the filtrate to 1600.0 L, control the temperature at 30℃, add R-(-)-camphor-10-sulfonic acid in batches, stir at 30℃ for 15 hours, and filter.

[0057] Add the filter cake and 1065.0 kg of ethanol to the reactor, maintain the temperature at 65°C and stir until dissolved. Cool to 40°C, add seed crystals, and then maintain the temperature at 45°C and stir for 3 hours. Reduce the temperature to 30°C in a gradient of 10°C / hour, and then stir at 30°C for 10 hours. Filter.

[0058] Add the filter cake and 475.0 kg of ethanol to the reactor, maintain the temperature at 70°C while stirring to dissolve, cool to 55°C, add seed crystals, then maintain the temperature at 60°C and stir for 3 hours. Reduce the temperature to 30°C in a gradient of 10°C / hour, and then stir at 30°C for 10 hours. Filter.

[0059] The filter cake and 295.0 kg of ethanol were added to a reaction vessel, and the mixture was stirred and dissolved at 75°C. The temperature was then lowered to 58°C, seed crystals were added, and the mixture was stirred at 60°C for 3 hours. The temperature was then gradually decreased to 30°C at a rate of 10°C / hour, and then stirred at 30°C for 10 hours. The mixture was then filtered. The filter cake was dried to obtain 26.6 kg of a white solid, 4-(1-hydroxy-2-aminoethyl)phenol R-(-)-camphor-10-sulfonate, with a chemical purity of 100.0% and a chiral purity of 100.0%, yielding 8.6%.

[0060] S2:

[0061] Add 230.0 kg of acetic acid and 22.0 kg of 4-(1-hydroxy-2-aminoethyl)phenol R-(-)-camphor-10-sulfonate, maintaining the temperature at 30°C. Add 6.6 kg of 68% concentrated nitric acid dropwise. After the addition is complete, continue the reaction for 2 hours, then filter. Mix the filter cake with 70.0 kg of ethanol, maintaining the temperature at 30°C, and stir for 5 hours. Filter and dry the filter cake to obtain 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%.

[0062] S3:

[0063] 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℃, add 48.0 kg of saturated sodium bicarbonate aqueous solution dropwise, stir for 15 hours after the addition is complete, filter, add the filter cake and 42.0 kg of ethanol to the reaction vessel, control the temperature at 30℃, stir for 5 hours, and filter. 91.0 kg of filter cake and process water were added to a reactor, followed by 12.0 kg of sodium bicarbonate and 16.2 kg of di-tert-butyl dicarbonate. The mixture was stirred at 35°C for 20 hours. The mixture was extracted three times with 32.0 kg of ethyl acetate. The ethyl acetate phases were combined and dried with anhydrous sodium sulfate. The dried organic phase was concentrated to 40 L, and 115.0 kg of petroleum ether was added dropwise. The mixture was stirred at 30°C for 8 hours, 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%.

[0064] Comparative Example 1

[0065] In step S1, D-(-)-tartaric acid was used; the remaining steps were the same as in Example 1. No significant separation effect was observed.

[0066] Comparative Example 2

[0067] In step S2, 75% concentrated nitric acid is added, and the remaining steps are the same as in Example 1.

[0068] The final obtained (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol had a chemical purity of 97.2%, a chiral purity of 98.3%, and a yield of 51.2%.

[0069] Comparative Example 3

[0070] In step S2, 50% concentrated nitric acid is added, and the remaining steps are the same as in Example 1.

[0071] The final obtained (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol had a chemical purity of 97.9%, a chiral purity of 98.9%, and a yield of 48.8%.

[0072] Comparative Example 4

[0073] In step S3, dichloromethane is used instead of ethyl acetate for extraction; the remaining steps are the same as in Example 1.

[0074] The final obtained (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol had a chemical purity of 97.6%, a chiral purity of 99.0%, and a yield of 52.6%.

[0075] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope 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: The substrate is added to an alcohol solvent, followed by an inorganic base, and then R-(-)-camphor-10-sulfonic acid to initiate a salt formation reaction, yielding product A. The substrate in S1 is 4-(1-hydroxy-2-aminoethyl)phenol hydrochloride, the alcohol solvent is one of methanol, ethanol, isopropanol or tert-butanol, and the inorganic base is one of sodium carbonate, potassium carbonate, cesium carbonate, lithium hydroxide, sodium hydroxide or potassium hydroxide. S2, Nitration: Product A is added to a solvent, and nitric acid is added dropwise to carry out the nitration reaction to obtain product B; S3. Boc Protection: Product B is added to a solvent, followed by the addition of an inorganic base and di-tert-butyl dicarbonate to react and yield (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol. The synthetic route is as follows. 。 2. The method for preparing (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol according to claim 1, characterized in that, In S1, the weight ratio of solvent to substrate is (5~25):1, the molar ratio of inorganic base to substrate is (0.95~1.05):1, and the molar ratio of R-(-)-camphor-10-sulfonic acid to substrate is 0.95:1.

05.

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

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

1.

5. The method for preparing (S)-4-[2-(Boc-amino)-1-hydroxyethyl]-2-nitrophenol according to claim 1, characterized in that, 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.

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

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