Preparation method of N-alpha-t-butyloxycarboryl-L-lysine

Abstract

The invention relates to a preparation method of N-alpha-t-butyloxycarboryl-L-lysine (N-alpha-t-butyloxycarboryl). The preparation method of the N-alpha-t-butyloxycarbonyl-L-lysine comprises the following steps: mixing L-lysine hydrochloride with hyperbranched aromatic borate, reacting under the action of a phosphate buffer solution and N, N-dimethylformamide to obtain an intermediate b, mixing the intermediate b with benzyl halide, reacting under the action of alkali and a solvent I to obtain an intermediate c, and reacting under the action of a solvent II to obtain the N-alpha-t-butyloxycarbonyl-L-lysine. The intermediate c, a phosphate buffer solution and N, N-dimethylformamide are mixed and then react to obtain an intermediate d, the intermediate d and di-tert-butyl dicarbonate ester are mixed and then react under the action of alkali and a second solvent to obtain an intermediate e, and the intermediate e and ferric chloride react in a third solvent to obtain the ferric chloride. The preparation method comprises the following steps: protecting alpha-amino and carboxyl by using L-lysine hydrochloride and hyperbranched aromatic borate, performing benzyl protection on epsilon-amino, performing boron removal protection, reacting alpha-amino with di-tert-butyl dicarbonate, and performing epsilon-aminobenzyl removal protection to obtain N-alpha-tert-butyloxycarboryl-L-lysine.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a method for preparing N-alpha-tert-butyloxycarbonyl-L-lysine. Background Art

[0002] Lysine is one of the essential amino acids that cannot be synthesized by the human body and animals. It is widely used in the food industry, feed industry, pharmaceutical industry and chemical industry.

[0003] Lysine is used as a pharmaceutical chemical intermediate or raw material, and usually needs to be protected by the ε-amino group. At present, the most common method for protecting lysine is to use copper ions to simultaneously protect the α-amino group and the carboxyl group, then use benzyl to protect the ε-amino group, and finally remove the complexed copper ions, protect the α-amino group with tert-butyloxycarbonyl, and then debenzylate the ε-amino group to obtain N-alpha-tert-butyloxycarbonyl-L-lysine. This method has the problems of long protection time, incomplete reaction and a lot of copper ion wastewater. Using 9-BBN as a complexing agent will result in a large amount of water and by-products, which is not environmentally friendly. Summary of the invention

[0004] The purpose of the present invention is to provide a method for preparing N-alpha-tert-butyloxycarbonyl-L-lysine to solve the technical problems of excessive copper ion wastewater when copper ions are used as complexing agents and a large amount of by-products when 9-BBN is used as a complexing agent.

[0005] In order to achieve the above purpose, the technical solution adopted by the present invention is:

[0006] A method for preparing N-alpha-tert-butyloxycarbonyl-L-lysine comprises the following steps:

[0007] S1: L-lysine hydrochloride is mixed with a hyperbranched aromatic borate ester and reacted in a phosphate buffer and N,N-dimethylformamide to obtain an intermediate b, as shown in Formula I;

[0008]

[0009] S2: After the intermediate b and the benzyl halide are mixed, they react under the action of a base and a solvent to obtain an intermediate c, and the reaction formula is shown in Formula II;

[0010]

[0011] S3: Intermediate c, phosphate buffer, and N,N-dimethylformamide are mixed and reacted to obtain intermediate d, and the reaction formula is shown in Formula III;

[0012]

[0013] S4: After the intermediate d is mixed with di-tert-butyl dicarbonate, the intermediate e is reacted under the action of a base and a solvent 2, and the reaction formula is shown in Formula IV;

[0014]

[0015] S5: Intermediate e reacts with ferric chloride in solvent three to obtain N-alpha-tert-butyloxycarbonyl-L-lysine, and the reaction formula is shown in Formula V;

[0016]

[0017] Furthermore, the structure of the hyperbranched aromatic borate ester described in S1 is shown in Formula VI,

[0018]

[0019] Furthermore, the mass ratio of L-lysine hydrochloride and hyperbranched aromatic borate described in S1 is 1:1.5-1:3; the mass ratio of L-lysine hydrochloride to N,N-dimethylformamide is 1:2-1:10; the volume ratio of phosphate buffer to N,N-dimethylformamide is 1:3; the reaction temperature is 25-40°C, and the reaction time is 0.5-1.5h.

[0020] Furthermore, the mass ratio of the intermediate b and the benzyl halide in S2 is 1:0.3 to 1:0.9; the mass ratio of the intermediate b and the base is 1:0.15 to 1:0.4; the mass ratio of the intermediate b and the solvent 1 is 1:2 to 1:10; the reaction temperature is 0 to 30°C, and the reaction time is 5 to 10 hours.

[0021] Furthermore, the benzyl halide described in S2 is one or more of benzyl chloride and benzyl bromide; the base is one or more of sodium carbonate, potassium carbonate, and triethylamine; and the solvent 1 is one or more of N-methylpyrrolidone, water, tetrahydrofuran, dimethyl sulfoxide, and N,N-dimethylformamide.

[0022] Furthermore, the mass ratio of the intermediate c described in S3 to N,N-dimethylformamide is 1:2 to 1:10; the volume ratio of N,N-dimethylformamide to phosphate buffer is 1:3; the reaction temperature is 25 to 40°C, and the reaction time is 0.5 to 1.5h.

[0023] Furthermore, in S4, the mass ratio of the intermediate d to di-tert-butyl dicarbonate is 1:0.95 to 1:1.5; the mass ratio of the intermediate d to the base is 1:0.4 to 1:1; the mass ratio of the intermediate d to the solvent 2 is 1:2 to 1:10; the reaction temperature is 25 to 35°C, and the reaction time is 2 to 4.5 hours.

[0024] Furthermore, the second solvent is one or more of methanol and acetonitrile; the base is one or more of tetramethylammonium hydroxide and tetrabutylammonium hydroxide.

[0025] Furthermore, the mass ratio of the intermediate e and ferric chloride in S5 is 1:0.3 to 1:1.05, and the mass ratio of the intermediate e to the solvent three is 1:3 to 1:6; the reaction temperature is 25 to 35°C, and the reaction time is 0.5 to 1.5h; the solvent three is one or more of dichloromethane, chloroform and petroleum ether.

[0026] Furthermore, the pH of the phosphate buffer in S1 and S3 is 7.4, and the phosphate buffer includes sodium dihydrogen phosphate and disodium hydrogen phosphate.

[0027] Beneficial effects of the present invention:

[0028] The invention uses L-lysine hydrochloride and hyperbranched aromatic borate to protect α-amino and carboxyl groups, then performs benzyl protection on ε-amino, then performs deboronization protection, and then reacts the α-amino with di-tert-butyl dicarbonate to remove the ε-amino benzyl protection to obtain N-alpha-tert-butyloxycarbonyl-L-lysine. The invention has high selectivity, mild reaction conditions, and hyperbranched aromatic borate can be recycled and reused, is environmentally friendly, and has good industrial application value.

[0029] Based on the existing preparation method, the present invention further studies and improves the synthesis conditions of N-alpha-tert-butyloxycarbonyl-L-lysine, creating conditions for industrialization. The use of hyperbranched aromatic borate complexing agent avoids the use of copper ions and 9-BBN with a large amount of wastewater, and can be recycled and reused environmentally friendly; the reaction selectivity is high, the generation of by-products is avoided, the reaction is carried out at room temperature, the conditions are mild, the operation is simple, it is more economical and green, meets the requirements of large-scale industrial production, and has good industrial application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is the high performance liquid chromatogram of N-alpha-tert-butyloxycarbonyl-L-lysine in Example 4. DETAILED DESCRIPTION

[0031] The present invention will be further described below in conjunction with the embodiments of the present invention and the accompanying drawings.

[0032] Hyperbranched aromatic borate (HB) preparation method is synthesized according to known methods:

[0033] Weigh resorcinol, boric acid, and ferric chloride in a molar ratio of 1:1:0.025 and mix to obtain a mixture, dissolve the mixture in N-methylpyrrolidone, and obtain a reaction solution after the mixture is completely dissolved. Add the reaction solution to a four-necked flask equipped with a stirring device, a reflux condenser, a water separator, and a nitrogen-passing device, and then add toluene to the four-necked flask. React at 90°C for 8 hours, then slowly heat up, replace the refluxed benzene with xylene, raise the reaction temperature of the system to 165°C for 8 hours, then slowly heat up and evaporate xylene. The system refluxes at 202°C for 8 hours, evaporates the solvent, and obtains a reddish-brown viscous substance. The obtained reddish-brown viscous substance continues to react at 37°C for 2 hours, then naturally warms to 40°C, adds acetone to the flask, and the substance on the inner wall of the flask is dissolved, then poured out and added with ether for precipitation, and repeated three times to obtain HB, the characteristic viscosity of HB is 0.38d L / g.

[0034] Phosphate buffer (NaPB): Dissolve 136.89 g sodium chloride, 6.8 g potassium chloride, 17.55 g disodium hydrogen phosphate, and 2.4 g potassium dihydrogen phosphate in distilled water and adjust the pH of the solution to 7.4 with hydrochloric acid.

[0035] Example 1

[0036] The preparation method of N-alpha-tert-butyloxycarbonyl-L-lysine of Example 1 comprises the following steps:

[0037] 16.4 g of HB was dissolved in 23 mL of N,N-dimethylformamide (DMF) to obtain solution 1, 10.9 g of L-lysine hydrochloride was dissolved in 7.6 mL of phosphate buffer with a pH of 7.4 and a concentration of 0.1 M to obtain solution 2, solution 1 was added to solution 2 at room temperature to obtain a mixed solution, after stirring at 25°C for 1.5 h, the mixed solution was poured into water and extracted with ethyl acetate three times, with a single use amount of 30 mL. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and eluted with methanol-water (3:1) for column chromatography to obtain 23.7 g of intermediate b, with a yield of 87%.

[0038] 23.7 g of intermediate b, 3.555 g of sodium carbonate and 52.8 mL of tetrahydrofuran (THF) were mixed to obtain solution three. 7.5 g of benzyl chloride was added to the stirring solution three at 0°C and monitored by thin layer chromatography (TLC). The solution was stirred at 0°C for 10 h and then extracted three times with dichloromethane, with a single amount of 50 mL. The organic phase was dried and evaporated to obtain a solid, which was eluted by column chromatography with hexane-ethyl acetate (2:1) to obtain 27.6 g of intermediate c with a yield of 95%.

[0039] Dissolve 27.6 g of intermediate c in 58.23 mL of DMF, add 165.6 mL of phosphate buffer with a pH of 7.4 and a concentration of 0.1 M at room temperature to obtain a mixture. After stirring at 37°C for 0.5 h, pour the mixture into water and filter, recover HB from the filter cake, and extract the filtrate three times with ethyl acetate, with a single use amount of 200 mL. Wash the organic layer with brine, dry with anhydrous sodium sulfate, and elute with methanol-water (3:1) for column chromatography to obtain 13 g of intermediate d with a yield of 98%.

[0040] 13g of intermediate d and 5.2g of tetramethylammonium hydroxide were added to 33.1mL of acetonitrile (MeCN), and 12.4g of di-tert-butyl dicarbonate (Boc)2O in MeCN solution was added dropwise at 0°C. After the addition was completed, the mixture was stirred for 30 minutes and then stirred at 25°C for 4.5h. The solvent was removed under reduced pressure, washed with 250mL of saturated sodium bicarbonate solution, and the aqueous phase was extracted three times with ether, with a single use amount of 50mL. The combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 17.9g of intermediate e with a yield of 96.6%.

[0041] 17.9 g of intermediate e, 40.5 mL of dichloromethane (DCM) and 5.4 g of ferric chloride were mixed and reacted at 25° C. for 1.5 h, the solvent was evaporated, and the mixture was extracted three times with ethyl acetate, with a single extraction amount of 50 mL. The organic phases were combined, concentrated under reduced pressure, slurried and concentrated with methyl tert-butyl ether, and dried to obtain 12.5 g of N-alpha-tert-butyloxycarbonyl-L-lysine with a purity of 99.3% and a yield of 95.5%.

[0042] The reaction pathway of N-alpha-tert-butyloxycarbonyl-L-lysine in Example 1 is shown in Formula VII:

[0043]

[0044] The preparation method of N-alpha-tert-butyloxycarbonyl-L-lysine of Example 2 comprises the following steps:

[0045] 21.8 g of HB was dissolved in 57.5 mL of DMF to obtain solution 1, 10.9 g of L-lysine hydrochloride was dissolved in 19.1 mL of phosphate buffer with a pH of 7.4 and a concentration of 0.1 M to obtain solution 2, solution 1 was added to solution 2 at room temperature to obtain a mixed solution, after stirring at 35°C for 1 hour, the mixed solution was poured into water and extracted with ethyl acetate three times, with a single use amount of 100 mL. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and eluted with methanol-water (3:1) for column chromatography to obtain 27.8 g of intermediate b, with a yield of 85%.

[0046] 27.8 g of intermediate b, 8.3 g of triethylamine and 114 mL of THF were mixed to obtain solution three. 13.9 g of benzyl chloride was added to the stirring solution three at 0°C and stirred at 10°C for 6.5 h (monitored by TLC). The mixture was then extracted three times with dichloromethane, with a single extraction volume of 200 mL. The organic phase was dried and evaporated to obtain a solid, which was eluted by column chromatography with hexane-ethyl acetate (2:1) to obtain 32.3 g of intermediate c with a yield of 95%.

[0047] 32.3 g of intermediate c was dissolved in 161.5 mL of DMF, and 484.5 mL of phosphate buffer with a pH of 7.4 and a concentration of 0.1 M was added at room temperature to obtain a mixture. After stirring at 25°C for 1 h, the mixture was poured into water and filtered, HB was recovered from the filter cake, and the filtrate was extracted twice with ethyl acetate, with a single use amount of 500 mL. The organic layer was washed with brine, dried with anhydrous sodium sulfate, and eluted with methanol-water (3:1) for column chromatography to obtain 15.2 g of intermediate d, with a yield of 98%.

[0048] 15.2g of intermediate d and 12.4g of tetramethylammonium hydroxide were added to 76mL of MeCN, and 18.4g of MeCN solution of di-tert-butyl dicarbonate was added dropwise at 0°C. After the addition was completed, the mixture was stirred for 30 minutes and then stirred at 30°C for 3h. The solvent was removed under reduced pressure, washed with 150mL of saturated sodium bicarbonate solution, and the aqueous phase was extracted three times with ether, with a single use amount of 50mL. The combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 19.9g of intermediate e with a yield of 96.5%.

[0049] 19.9 g of intermediate e, 96.64 mL of DCM and 10.4 g of ferric chloride were mixed and reacted at 30° C. for 1 h, the solvent was evaporated, and the mixture was extracted three times with ethyl acetate, with a single extraction amount of 50 mL. The organic phases were combined, concentrated under reduced pressure, slurried and concentrated with methyl tert-butyl ether, and dried to obtain 14.8 g of N-alpha-tert-butyloxycarbonyl-L-lysine with a purity of 99.8% and a yield of 97.4%.

[0050] Example 3

[0051] The preparation method of N-alpha-tert-butyloxycarbonyl-L-lysine of Example 3 comprises the following steps:

[0052] 32.7 g of HB was dissolved in 109 mL of DMF to obtain solution 1, 10.9 g of L-lysine hydrochloride was dissolved in 36.3 mL of phosphate buffer with a pH of 7.4 and a concentration of 0.1 M to obtain solution 2, solution 1 was added to solution 2 at room temperature to obtain a mixed solution, after stirring at 40°C for 0.5 h, the mixed solution was poured into water and extracted with ethyl acetate three times, with a single use amount of 200 mL. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and eluted with methanol-water (3:1) for column chromatography to obtain 19.9 g of intermediate b, with a yield of 83%.

[0053] 19.9 g of intermediate b, 7.9 g of potassium carbonate and 126 mL of N-methylpyrrolidone (NMP) were mixed to obtain solution three. 17.9 g of benzyl bromide was added to the stirring solution three at 0°C, and stirred at 30°C for 5 h (TLC monitoring). Then, the solution was extracted three times with dichloromethane, with a single amount of 200 mL. The organic phase was dried and evaporated to obtain a solid, which was eluted by column chromatography with hexane-ethyl acetate (2:1) to obtain 23.5 g of intermediate c with a yield of 96.3%.

[0054] Dissolve 23.5 g of intermediate c in 235 mL of DMF, add 705 mL of phosphate buffer with a pH of 7.4 and a concentration of 0.1 M at room temperature to obtain a mixture. After stirring at 40°C for 0.5 h, pour the mixture into water and filter, recover HB from the filter cake, and extract the filtrate twice with ethyl acetate, with a single use amount of 500 mL. Wash the organic layer with brine, dry with anhydrous sodium sulfate, and elute with methanol-water (3:1) on the column chromatography to obtain 10.9 g of intermediate d, with a yield of 97%.

[0055] 10.9 g of intermediate d and 10.9 g of tetrabutylammonium hydroxide were added to 109 mL of MeCN, and 16.4 g of MeCN solution of di-tert-butyl dicarbonate was added dropwise at 0 ° C. After the addition was completed, it was stirred for 30 minutes and stirred at 35 ° C for 2 hours. The solvent was removed under reduced pressure, washed with 150 mL of saturated sodium bicarbonate solution, and the aqueous phase was extracted three times with ether, with a single use amount of 50 mL. The combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 14.4 g of intermediate e, with a yield of 97.5%.

[0056] 14.4 g of intermediate e, 90.6 mL of petroleum ether and 15.8 g of ferric chloride were mixed and reacted at 35° C. for 0.5 h, the solvent was evaporated, and the mixture was extracted three times with ethyl acetate, with a single extraction amount of 100 mL. The organic phases were combined and concentrated under reduced pressure, slurried and concentrated with methyl tert-butyl ether, and dried to obtain 10.7 g of N-alpha-tert-butyloxycarbonyl-L-lysine with a purity of 99.8% and a yield of 97%.

[0057] Example 4

[0058] The preparation method of N-alpha-tert-butyloxycarbonyl-L-lysine of Example 4 comprises the following steps:

[0059] 9 g of HB was dissolved in 30 mL of DMF to obtain solution 1, 6 g of L-lysine hydrochloride was dissolved in 10 mL of phosphate buffer with a pH of 7.4 and a concentration of 0.1 M to obtain solution 2, solution 1 was added to solution 2 at room temperature to obtain a mixed solution, after stirring at 35°C for 1 hour, the mixed solution was poured into water and extracted with ethyl acetate three times, with a single use amount of 100 mL. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and eluted with methanol-water (3:1) for column chromatography to obtain 10.8 g of intermediate b, with a yield of 81.8%.

[0060] 10.8 g of intermediate b, 4.32 g of triethylamine and 114 mL of THF were mixed to obtain solution three. 7.5 g of benzyl bromide was added to the stirring solution three at 0°C, and stirred at 10°C for 6.5 h (monitored by TLC). The solution was then extracted three times with dichloromethane, with a single extraction volume of 200 mL. The organic phase was dried and evaporated to obtain a solid, which was eluted by column chromatography with hexane-ethyl acetate (2:1) to obtain 12.2 g of intermediate c with a yield of 92%.

[0061] Dissolve 12.2 g of intermediate c in 36.6 mL of DMF, add 109.8 mL of phosphate buffer with a pH of 7.4 and a concentration of 0.1 M at room temperature to obtain a mixture. After stirring at 25°C for 0.5 h, pour the mixture into water and filter, recover HB from the filter cake, and extract the filtrate twice with ethyl acetate, with a single use amount of 500 mL. Wash the organic layer with brine, dry with anhydrous sodium sulfate, and elute with methanol-water (3:1) on the column chromatography to obtain 5.7 g of intermediate d, with a yield of 97.5%.

[0062] 5.7 g of intermediate d and 2.8 g of tetramethylammonium hydroxide were added to 17 mL of MeCN, and 5.7 g of MeCN solution of di-tert-butyl dicarbonate was added dropwise at 0 ° C. After the addition was completed, it was stirred for 30 minutes and stirred at 30 ° C for 3 hours. The solvent was removed under reduced pressure, washed with 150 mL of saturated sodium bicarbonate solution, and the aqueous phase was extracted three times with ether, with a single use amount of 50 mL. The combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 7.34 g of intermediate e, with a yield of 95.5%.

[0063] 7.34 g of intermediate e, 23 mL of DCM and 3.3 g of ferric chloride were mixed and reacted at 30°C for 1 h. The solvent was evaporated and extracted three times with ethyl acetate, with a single amount of 50 mL. The organic phases were combined and concentrated under reduced pressure, slurried and concentrated with methyl tert-butyl ether, and dried to obtain 5.5 g of N-alpha-tert-butyloxycarbonyl-L-lysine with a purity of 99.5% and a yield of 97.6%.

[0064] Example 5

[0065] The preparation method of N-alpha-tert-butyloxycarbonyl-L-lysine of Example 5 comprises the following steps:

[0066] 21.8 g of HB was dissolved in 57.5 mL of DMF to obtain solution 1, 10.9 g of L-lysine hydrochloride was dissolved in 19.1 mL of phosphate buffer with a pH of 7.4 and a concentration of 0.1 M to obtain solution 2, solution 1 was added to solution 2 at room temperature to obtain a mixed solution, after stirring at 35 ° C for 1 hour, the mixed solution was poured into water and extracted with ethyl acetate three times, with a single use amount of 100 mL. The organic layer was washed with brine, dried with anhydrous sodium sulfate, and eluted with methanol-water (3:1) for column chromatography to obtain 23.3 g of intermediate b, with a yield of 96.8%.

[0067] 23.3 g of intermediate b, 6.1 g of triethylamine and 123 mL of THF were mixed to obtain solution three. 10.2 g of benzyl chloride was added to the stirring solution three at 0°C and stirred at 10°C for 6.5 h (TLC monitoring). The mixture was then extracted three times with dichloromethane, with a single extraction volume of 200 mL. The organic phase was dried and evaporated to obtain a solid, which was eluted by column chromatography with hexane-ethyl acetate (2:1) to obtain 28.2 g of intermediate c with a yield of 98.9%.

[0068] Dissolve 28.2 g of intermediate c in 146 mL of DMF, add 438 mL of phosphate buffer with a pH of 7.4 and a concentration of 0.1 M at room temperature to obtain a mixture. After stirring at 25°C for 0.5 h, pour the mixture into water and filter, recover HB from the filter cake, and extract the filtrate twice with ethyl acetate, with a single use amount of 500 mL. Wash the organic layer with brine, dry with anhydrous sodium sulfate, and elute with methanol-water (3:1) on the column chromatography to obtain 13.3 g of intermediate d, with a yield of 98.5%.

[0069] 13.3 g of intermediate d and 11.3 g of tetramethylammonium hydroxide were added to 34.62 mL of methanol, and 16.8 g of MeCN solution of di-tert-butyl dicarbonate was added dropwise at 0 ° C. After the addition was completed, it was stirred for 30 minutes and stirred at 30 ° C for 3 hours. The solvent was removed under reduced pressure, washed with 150 mL of saturated sodium bicarbonate solution, and the aqueous phase was extracted three times with ether, with a single use amount of 50 mL. The combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 17.8 g of intermediate e, with a yield of 98.5%.

[0070] 17.8 g of intermediate e, 96 mL of DCM and 9.6 g of ferric chloride were mixed and reacted at 30°C for 1 h. The solvent was evaporated and extracted three times with ethyl acetate, with a single amount of 50 mL. The organic phases were combined and concentrated under reduced pressure, slurried and concentrated with methyl tert-butyl ether, and dried to obtain 13.4 g of N-alpha-tert-butyloxycarbonyl-L-lysine with a purity of 99.7% and a yield of 98.5%.

Claims

1. A method for preparing N-alpha-tert-butyloxycarbonyl-L-lysine, characterized in that: The following steps are involved: S1: L-lysine hydrochloride is mixed with a hyperbranched aromatic borate, and then reacted in a phosphate buffer and N,N-dimethylformamide to obtain an intermediate b, as shown in Formula I; S2: After the intermediate b and the benzyl halide are mixed, they react under the action of a base and a solvent to obtain an intermediate c, and the reaction formula is shown in Formula II; S3: Intermediate c, phosphate buffer, and N,N-dimethylformamide are mixed and reacted to obtain intermediate d, and the reaction formula is shown in Formula III; S4: After the intermediate d is mixed with di-tert-butyl dicarbonate, the intermediate e is reacted under the action of a base and a solvent 2, and the reaction formula is shown in Formula IV; S5: Intermediate e reacts with ferric chloride in solvent three to obtain N-alpha-tert-butyloxycarbonyl-L-lysine, and the reaction formula is shown in Formula V; 2. The method for preparing N-alpha-tert-butyloxycarbonyl-L-lysine according to claim 1, characterized in that: The structure of the hyperbranched aromatic borate ester described in S1 is shown in Formula VI, 3. The method for preparing N-alpha-tert-butyloxycarbonyl-L-lysine according to claim 1, characterized in that: The mass ratio of L-lysine hydrochloride and hyperbranched aromatic borate described in S1 is 1:1.5-1:3; the mass ratio of L-lysine hydrochloride to N,N-dimethylformamide is 1:2-1:10; the volume ratio of phosphate buffer to N,N-dimethylformamide is 1:3; the reaction temperature is 25-40°C, and the reaction time is 0.5-1.5h.

4. The method for preparing N-alpha-tert-butyloxycarbonyl-L-lysine according to claim 1, characterized in that: The mass ratio of the intermediate b and the benzyl halide in S2 is 1:0.3 to 1:0.9; the mass ratio of the intermediate b and the base is 1:0.15 to 1:0.4; the mass ratio of the intermediate b and the solvent 1 is 1:2 to 1:10; the reaction temperature is 0 to 30°C, and the reaction time is 5 to 10 hours.

5. The method for preparing N-alpha-tert-butyloxycarbonyl-L-lysine according to claim 1 or 4, characterized in that: The benzyl halide described in S2 is one or more of benzyl chloride and benzyl bromide; the base is one or more of sodium carbonate, potassium carbonate, and triethylamine; the solvent one is one or more of N-methylpyrrolidone, water, tetrahydrofuran, dimethyl sulfoxide, and N,N-dimethylformamide.

6. The method for preparing N-alpha-tert-butyloxycarbonyl-L-lysine according to claim 1, characterized in that: The mass ratio of the intermediate c described in S3 to N,N-dimethylformamide is 1:2 to 1:10; the volume ratio of N,N-dimethylformamide to phosphate buffer is 1:3; the reaction temperature is 25 to 40°C, and the reaction time is 0.5 to 1.5h.

7. The method for preparing N-alpha-tert-butyloxycarbonyl-L-lysine according to claim 1, characterized in that: The mass ratio of the intermediate d and di-tert-butyl dicarbonate in S4 is 1:0.95 to 1:1.5; the mass ratio of the intermediate d and the base is 1:0.4 to 1:1; the mass ratio of the intermediate d and the solvent 2 is 1:2 to 1:10; the reaction temperature is 25 to 35°C, and the reaction time is 2 to 4.5h.

8. The method for preparing N-alpha-tert-butyloxycarbonyl-L-lysine according to claim 1 or 7, characterized in that: The second solvent is one or more of methanol and acetonitrile; the base is one or more of tetramethylammonium hydroxide and tetrabutylammonium hydroxide.

9. The method for preparing N-alpha-tert-butyloxycarbonyl-L-lysine according to claim 1, characterized in that: The mass ratio of the intermediate e and ferric chloride in S5 is 1:0.3 to 1:1.05, and the mass ratio of the intermediate e to the solvent three is 1:3 to 1:6; the reaction temperature is 25 to 35°C, and the reaction time is 0.5 to 1.5h; the solvent three is one or more of dichloromethane, chloroform and petroleum ether.

10. The method for preparing N-alpha-tert-butyloxycarbonyl-L-lysine according to claim 1, characterized in that: The pH of the phosphate buffer in S1 and S3 is 7.4, and the phosphate buffer comprises sodium dihydrogen phosphate and disodium hydrogen phosphate.

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