CN113979886B - Protective amino acid with side chain being amide and preparation method thereof - Google Patents
Protective amino acid with side chain being amide and preparation method thereof Download PDFInfo
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- CN113979886B CN113979886B CN202111241132.XA CN202111241132A CN113979886B CN 113979886 B CN113979886 B CN 113979886B CN 202111241132 A CN202111241132 A CN 202111241132A CN 113979886 B CN113979886 B CN 113979886B
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- amino acid
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- amide
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- 150000001413 amino acids Chemical class 0.000 title claims abstract description 44
- 150000001408 amides Chemical class 0.000 title claims abstract description 31
- 230000001681 protective effect Effects 0.000 title claims abstract description 5
- 238000002360 preparation method Methods 0.000 title abstract description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 93
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 46
- 239000012043 crude product Substances 0.000 claims abstract description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 28
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000000243 solution Substances 0.000 claims abstract description 16
- 239000000047 product Substances 0.000 claims abstract description 14
- 238000003756 stirring Methods 0.000 claims abstract description 14
- 238000002425 crystallisation Methods 0.000 claims abstract description 10
- 230000008025 crystallization Effects 0.000 claims abstract description 10
- 230000001105 regulatory effect Effects 0.000 claims abstract description 9
- 239000011259 mixed solution Substances 0.000 claims abstract description 6
- 238000001914 filtration Methods 0.000 claims abstract description 5
- 239000013078 crystal Substances 0.000 claims abstract description 3
- 229940024606 amino acid Drugs 0.000 claims description 38
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 13
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
- 229960000583 acetic acid Drugs 0.000 claims description 8
- 239000012362 glacial acetic acid Substances 0.000 claims description 8
- LZTRCELOJRDYMQ-UHFFFAOYSA-N triphenylmethanol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(O)C1=CC=CC=C1 LZTRCELOJRDYMQ-UHFFFAOYSA-N 0.000 claims description 7
- 229930182816 L-glutamine Natural products 0.000 claims description 6
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Chemical compound OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 4
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 4
- 229960001230 asparagine Drugs 0.000 claims description 3
- DCXYFEDJOCDNAF-UWTATZPHSA-N D-Asparagine Chemical compound OC(=O)[C@H](N)CC(N)=O DCXYFEDJOCDNAF-UWTATZPHSA-N 0.000 claims description 2
- 229930182846 D-asparagine Natural products 0.000 claims description 2
- ZDXPYRJPNDTMRX-GSVOUGTGSA-N D-glutamine Chemical compound OC(=O)[C@H](N)CCC(N)=O ZDXPYRJPNDTMRX-GSVOUGTGSA-N 0.000 claims description 2
- 229930195715 D-glutamine Natural products 0.000 claims description 2
- 125000003338 L-glutaminyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C(=O)N([H])[H] 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 7
- 239000012535 impurity Substances 0.000 abstract description 7
- 230000007547 defect Effects 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 23
- 238000000746 purification Methods 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000007788 liquid Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 6
- 239000003513 alkali Substances 0.000 description 6
- 239000012264 purified product Substances 0.000 description 6
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 5
- 239000012046 mixed solvent Substances 0.000 description 5
- BRRPJQYCERAMFI-HXUWFJFHSA-N (2r)-2-azaniumyl-4-oxo-4-(tritylamino)butanoate Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(NC(=O)C[C@@H]([NH3+])C([O-])=O)C1=CC=CC=C1 BRRPJQYCERAMFI-HXUWFJFHSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- XIFFJPJZPDCOJH-UHFFFAOYSA-N 2-azaniumyl-5-oxo-5-(tritylamino)pentanoate Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(NC(=O)CCC(N)C(O)=O)C1=CC=CC=C1 XIFFJPJZPDCOJH-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 150000001242 acetic acid derivatives Chemical class 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- XIFFJPJZPDCOJH-OAQYLSRUSA-N (2r)-2-azaniumyl-5-oxo-5-(tritylamino)pentanoate Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(NC(=O)CC[C@@H]([NH3+])C([O-])=O)C1=CC=CC=C1 XIFFJPJZPDCOJH-OAQYLSRUSA-N 0.000 description 1
- SPSSULHKWOKEEL-UHFFFAOYSA-N 2,4,6-trinitrotoluene Chemical compound CC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O SPSSULHKWOKEEL-UHFFFAOYSA-N 0.000 description 1
- BRRPJQYCERAMFI-UHFFFAOYSA-N 2-azaniumyl-4-oxo-4-(tritylamino)butanoate Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(NC(=O)CC(N)C(O)=O)C1=CC=CC=C1 BRRPJQYCERAMFI-UHFFFAOYSA-N 0.000 description 1
- SGKPDOQKJBOJTE-UHFFFAOYSA-N CC(=O)NC(=O)CCC(N)C(O)=O Chemical compound CC(=O)NC(=O)CCC(N)C(O)=O SGKPDOQKJBOJTE-UHFFFAOYSA-N 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- -1 N' - (acetyl) -D-asparagine Chemical compound 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000010364 biochemical engineering Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
- C07C231/24—Separation; Purification
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a protective amino acid with an amide side chain and a preparation method thereof, comprising the following steps: s1, adding a crude product of protected amino acid with an amide side chain into a mixed solution of tetrahydrofuran and ethyl acetate, stirring, and then adding hydrochloric acid to dissolve the crude product; s2, after the crude product is dissolved, regulating the pH value of a solution system to 6-7, and crystallizing the solution system to precipitate crystals; and S3, after crystallization is completed, obtaining a purified protected amino acid product with an amide side chain through centrifugal filtration. According to the invention, the produced protected amino acid crude product with the side chain of amide is dissolved in hydrochloric acid in a tetrahydrofuran/ethyl acetate solution system, and then crystallized and centrifuged, so that the high-purity protected amino acid product is finally obtained, the removal effect of acetylated impurities is excellent, the preparation period is short, the material consumption is low, and the defects of the existing preparation method are overcome.
Description
Technical Field
The invention relates to the technical field of biochemical engineering, in particular to a protective amino acid with an amide side chain and a preparation method thereof.
Background
At present, the industrial production of N '- (trityl) -L-glutamine is obtained by taking L-glutamine as a raw material and reacting and synthesizing the L-glutamine under the condition of glacial acetic acid, trityl alcohol, acetic anhydride and acid as catalysts, wherein the synthesis process inevitably generates 0.5-1w% of N' - (acetyl) -L-glutamine. For the purification treatment of N' - (trityl) -L-glutamine, a method is generally adopted in which water is firstly used for stirring, centrifugation is then used for stirring with ethyl acetate, centrifugation is then used for repeating the steps for purification. However, this purification process has poor purification effect, long cycle, relatively high cost, low production efficiency, and large residual N '- (acetyl) -L-glutamine, large product loss, inability to obtain high purity N' - (trityl) -L-glutamine, difficulty in making the impurity content of N '- (acetyl) -L-glutamine less than 0.1w%, and extremely poor removal effect of N' - (acetyl) -L-glutamine.
Disclosure of Invention
The invention aims at: aiming at the problems, the invention provides the protected amino acid with the side chain of amide and the preparation method thereof.
The technical scheme adopted by the invention is as follows: a method for purifying a protected amino acid having an amide side chain, comprising the steps of:
s1, adding a crude product of protected amino acid with an amide side chain into a mixed solution of tetrahydrofuran and ethyl acetate, stirring, and then adding hydrochloric acid to dissolve the crude product;
S2, after the crude product is dissolved, regulating the pH value of a solution system to 6-7, and crystallizing the solution system to precipitate crystals;
and S3, after crystallization is completed, obtaining a purified protected amino acid product with an amide side chain through centrifugal filtration.
In the invention, the prepared protected amino acid crude product with the side chain of amide is dissolved in tetrahydrofuran/ethyl acetate solution system, and then hydrochloric acid is added to adjust the pH value to 6-7 for crystallization, and the high-purity protected amino acid product is obtained after centrifugation (the protected amino acid has excellent solubility in tetrahydrofuran, tetrahydrofuran cannot be used alone, otherwise, the target product is difficult to crystallize and has extremely high loss), and the removal effect of acetylated impurities is extremely good, for example, when the protected amino acid crude product is N ' - (trityl) -L-glutamine with the purity of 60-70% (percent is in mass fraction), the purity of N ' - (trityl) -L-glutamine reaches 99.5w%, the impurity content of N ' - (acetyl) -L-glutamine is less than 0.1w%, the removal effect is extremely good, meanwhile, the purification period is short, repeated operation is not needed, the waste liquid production amount is small, the cost advantage is outstanding, and the defects existing in the existing purification method are overcome.
In the invention, the mass ratio of the tetrahydrofuran to the ethyl acetate is 0.5-1:10.
In the invention, the mass ratio of the crude product of the protected amino acid to the mixed solution of tetrahydrofuran and ethyl acetate is 1:3.
Further, in S1, the concentration of hydrochloric acid is 30%, and the addition amount is 1-1.05 times of the quality of the crude product of the protected amino acid.
In the invention, the crude product of the protected amino acid with the side chain being amide is obtained by reacting and synthesizing the amino acid with the side chain being amide in the presence of glacial acetic acid, trityl alcohol, acetic anhydride and acid. The protected amino acid crude product with the side chain of amide can be obtained by the existing commonly used synthesis method without changing the existing crude product preparation method.
Further, the mass ratio of amino acid with amide as side chain, glacial acetic acid, trityl alcohol, acetic anhydride and sulfuric acid is 1:20:2:1:0.8.
In the present invention, the amino acid having an amide side chain is L-glutamine, D-glutamine, DL-asparagine, D-asparagine or L-asparagine, and the corresponding synthetic protected amino acid is N ' - (trityl) -L-glutamine, N ' - (trityl) -D-glutamine, N ' - (trityl) -DL-asparagine, N ' - (trityl) -D-asparagine or N ' - (trityl) -L-asparagine.
The invention also comprises a preparation method of the protected amino acid with the side chain of amide, which comprises the following steps:
S1, reacting amino acid with an amide as a side chain in the presence of glacial acetic acid, tritol, acetic anhydride and acid to synthesize a protected amino acid crude product; the mass ratio of amino acid with amide as side chain, glacial acetic acid, triphenyl methanol, acetic anhydride and sulfuric acid is 1:20:2:1:0.8.;
S2, adding the crude product of the protected amino acid into a mixed solution of tetrahydrofuran and ethyl acetate, stirring, and then adding hydrochloric acid to dissolve the crude product; the mass ratio of the tetrahydrofuran to the ethyl acetate is 0.5-1:10;
s3, after the crude product is dissolved, regulating the pH value of the solution system to 6-7, and after crystallization is completed, centrifugally filtering to obtain the product.
The invention also comprises a protected amino acid with the side chain of amide, and the protected amino acid with the side chain of amide is prepared by the preparation method.
In summary, due to the adoption of the technical scheme, the beneficial effects of the invention are as follows: according to the invention, the prepared protected amino acid crude product with the side chain of amide is dissolved in hydrochloric acid in a tetrahydrofuran/ethyl acetate solution system, and then crystallized and centrifuged, so that a high-purity protected amino acid product is finally obtained, the removal effect of acetylated impurities is excellent, the preparation period is short, the material consumption is less, the defects of the existing preparation method are overcome, and the method is particularly suitable for industrial mass production of protected amino acid.
Detailed Description
The present invention will be described in further detail with reference to the following examples in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
Example 1 preparation of crude (N' - (triphenylmethyl) -L-glutamine)
A preparation method of N' - (trityl) -L-glutamine, comprising the following steps:
S1, adding 588g of glacial acetic acid and 29.4g of acetic anhydride into a dry 2L three-mouth bottle, stirring, adding 23.5g of sulfuric acid, keeping the temperature at 25-35 ℃, adding 58.8g of triphenylmethanol and 29.4g of L-glutamine (L-Gln), and reacting for 3 hours at 30-35 ℃;
S2, adding 250g of pure water at the temperature of 0 ℃ into the bottle, adding liquid alkali to adjust the pH value to 6-7, stirring and crystallizing for 2 hours, and filtering to obtain a crude product of N' - (trityl) -L-glutamine.
The crude N '- (trityl) -L-glutamine product was 66w% pure, and the N' - (acetyl) -L-glutamine content was 0.9w%.
Example 2 (ethyl acetate purification method)
Using the crude N' - (trityl) -L-glutamine obtained in example 1, the ethyl acetate purification process included the following steps:
s1, taking 50g of crude product of N' - (trityl) -L-glutamine, adding 200g of purified water, stirring and centrifuging;
s2, adding 200g of ethyl acetate, stirring and then centrifugally separating;
S3, repeating the operation of S1 and S2 for 3 times to obtain a purified N' - (trityl) -L-glutamine product.
Example 3
Using the crude N' - (trityl) -L-glutamine obtained in example 1, the ethanol/ethyl acetate purification process included the following steps:
S1, 50g of crude product of N' - (trityl) -L-glutamine, adding into a mixed solvent system of ethanol and ethyl acetate with 150g of stirring, and then dissolving the crude product with hydrochloric acid, wherein the mass ratio of the ethanol to the ethyl acetate is 1: 10;
S2, regulating the pH value of the solution system to 6-7 by using liquid alkali, and centrifugally separating after crystallization is finished to obtain a purified product.
Example 4
Using the crude N' - (trityl) -L-glutamine obtained in example 1, the methanol/ethyl acetate purification process comprises the steps of:
s1, 50g of crude product of N' - (trityl) -L-glutamine, adding into 150g of mixed solvent system of methanol and ethyl acetate, stirring, and then dissolving with hydrochloric acid, wherein the mass ratio of the methanol to the ethyl acetate is 1: 10;
S2, regulating the pH value of the solution system to 6-7 by using liquid alkali, and centrifugally separating after crystallization is finished to obtain a purified product.
Example 5
Example 5 is the same as example 4 except that the operation is repeated 4 times on the obtained purified product to obtain a high-purity N' - (trityl) -L-glutamine product.
Example 6
Using the crude N' - (trityl) -L-glutamine obtained in example 1, the tetrahydrofuran/ethyl acetate purification process included the following steps:
S1, 50g of crude product of N' - (trityl) -L-glutamine, adding 150g of tetrahydrofuran/ethyl acetate mixed solvent system, stirring, and then dissolving the crude product with hydrochloric acid, wherein the mass ratio of tetrahydrofuran to ethyl acetate is 1:10;
S2, regulating the pH value of the solution system to 6-7 by using liquid alkali, and centrifugally separating after crystallization is finished to obtain a purified product.
Example 7
The preparation method of the N '- (trityl) -DL-glutamine crude product is the same as that of the N' - (trityl) -L-glutamine crude product, and is not repeated herein, the N '- (trityl) -DL-glutamine crude product with the purity of 70w% is directly adopted in the embodiment, the N' - (acetyl) -DL-glutamine content is 0.6w%, and the tetrahydrofuran/ethyl acetate purification method comprises the following steps:
S1, 50g of crude product of N' - (trityl) -DL-glutamine, adding into 150g of mixed solvent system of tetrahydrofuran and ethyl acetate, stirring, and then dissolving with hydrochloric acid, wherein the mass ratio of tetrahydrofuran to ethyl acetate is 1:10;
S2, regulating the pH value of the solution system to 6-7 by using liquid alkali, and centrifugally separating after crystallization is finished to obtain a purified product.
Example 8
The preparation method of the N '- (trityl) -D-asparagine crude product is the same as that of the N' - (trityl) -L-glutamine crude product, and is not repeated herein, the crude product of the N '- (trityl) -D-asparagine with the purity of 65w% is directly adopted in the example, the content of the N' - (acetyl) -D-asparagine is 0.8w%, and the purification method of tetrahydrofuran/ethyl acetate comprises the following steps:
s1, 50g of crude product of N' - (trityl) -D-asparagine is added into 150g of mixed solvent system of tetrahydrofuran and ethyl acetate, stirred, and then dissolved by hydrochloric acid, wherein the mass ratio of tetrahydrofuran to ethyl acetate is 1:10;
S2, regulating the pH value of the solution system to 6-7 by using liquid alkali, and centrifugally separating after crystallization is finished to obtain a purified product.
Test results
The results of the tests of the products obtained in examples 1 to 8 above are shown in Table 1:
TABLE 1 Main detection data for the products obtained in examples 1-8
In table 1, the purity and the method for detecting the acetylated impurities were measured by high performance liquid chromatography under the following conditions:
stationary phase: octadecylsilane chemically bonded silica 5 μm 4.6 x 150mm;
mobile phase:
mobile phase a: trifluoroacetic acid: water=1:1000
Mobile phase B: trifluoroacetic acid: acetonitrile=1:1000;
Mobile phase gradient:
| Time min | Mobile phase a (%) | Mobile phase B (%) |
| 0 | 50 | 50 |
| 30 | 0 | 100 |
| 35 | 0 | 100 |
| 35.1 | 50 | 50 |
| Post run for 5min | 50 | 50 |
Flow rate: 1ml/min;
Detecting a wavelength; 220nm;
As can be obtained from the table 1, the purification method of the invention can lead the content of the acetylated impurity to be less than 0.1w percent, has excellent removal effect, simultaneously has short purification period, does not need repeated operation, has little waste liquid production amount and outstanding cost advantage, and overcomes the defects of the prior purification method.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, and alternatives falling within the spirit and principles of the invention.
Claims (2)
1. A method for purifying a protected amino acid having an amide side chain, comprising the steps of:
S1, adding a crude product of protected amino acid with an amide side chain into a mixed solution of tetrahydrofuran and ethyl acetate, stirring, and then adding hydrochloric acid to dissolve the crude product; wherein the mass ratio of the tetrahydrofuran to the ethyl acetate is 0.5-1:10, the mass ratio of the crude product of the protected amino acid to the mixed solution of tetrahydrofuran and ethyl acetate is 1:3, the concentration of hydrochloric acid is 30%, and the addition amount is 1-1.05 times of the mass of the crude product of the protected amino acid; the crude product of the protective amino acid with the side chain of amide is synthesized by reacting amino acid with the side chain of amide in the presence of glacial acetic acid, trityl alcohol, acetic anhydride and sulfuric acid, and the amino acid with the side chain of amide is L-glutamine, D-glutamine, DL-asparagine, D-asparagine or L-asparagine;
S2, after the crude product is dissolved, regulating the pH value of a solution system to 6-7, and crystallizing the solution system to precipitate crystals;
and S3, after crystallization is completed, obtaining a purified protected amino acid product with an amide side chain through centrifugal filtration.
2. The method for purifying an amino acid protected with an amide as claimed in claim 1, wherein the mass ratio of the amino acid with an amide as the side chain, glacial acetic acid, trityl alcohol, acetic anhydride and sulfuric acid is 1:20:2:1:0.8.
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