CN109912499B - Abamebactam intermediate and preparation method thereof - Google Patents

Abamebactam intermediate and preparation method thereof Download PDF

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CN109912499B
CN109912499B CN201711317983.1A CN201711317983A CN109912499B CN 109912499 B CN109912499 B CN 109912499B CN 201711317983 A CN201711317983 A CN 201711317983A CN 109912499 B CN109912499 B CN 109912499B
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孙敏
雷显涛
杨飞
王超原
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Shanghai Institute of Materia Medica of CAS
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Abstract

The present invention provides a process for the preparation of a compound of formula (I) comprising the steps of: 1) preparing a compound of formula (III) from a compound of formula (II); 2) preparing a compound of formula (IV) from a compound of formula (III); 3) preparing a compound of formula (I) from a compound of formula (IV); wherein P is1Representing a protective group for a carboxylic acid function, P2Represents a protecting group for a hydroxylamine function, P3Represents a protecting group for an amine group. The reaction route is as follows:

Description

Abamebactam intermediate and preparation method thereof
Technical Field
The invention belongs to the field of drug synthesis, and particularly relates to a preparation method of an avibactam intermediate (S) -5-benzyloxy amino piperidine-2-benzyl carboxylate.
Background
Abamebactam (Avibactam, NXL-104) is a novel beta-lactamase inhibitor with a non-beta-lactam structure, has a chemical name of [ (1R,2S,5R) -2- (aminocarbonyl) -7-oxo-1, 6-diazabicyclo [3.2.1] oct-6-yl ] sulfuric acid monoester, is clinically applied in the form of a sodium salt thereof, and has a structure shown as follows. In 2 months 2015, the FDA in the united states approved a new antibiotic, ceftazidime-avibactam (sodium salt), marketed under the trade name Avycaz, for the treatment of complex intraperitoneal infections and complex urinary tract infections, applicable to patients with renal infections (pyelonephritis) with limited or no alternative treatment regimens.
Figure BDA0001504171930000011
The compound of formula (I) is a key intermediate for the synthesis of avibactam, wherein P1 represents a protecting group for a carboxylic acid function and P2 represents a protecting group for a hydroxylamine function.
Figure BDA0001504171930000012
CN102056901A discloses a preparation method of (2S,5R) -5-benzyloxyaminopiperidine-2-carboxylic acid benzyl ester (g), which is an intermediate compound, comprising the steps of using (S) protected pyroglutamic acid (a) as a starting material, performing ring opening by the action of trimethylsulfoxonium iodide to obtain a compound (b), sequentially using a reagent for generating HCl to obtain a compound (c), performing treatment with a hydroxylamine derivative to obtain a compound (d), deprotecting amine by the action of acid to obtain a compound (e), performing cyclization by the action of a base to obtain a compound (f), and then reducing oxime function by the action of a reducing agent to obtain a compound (g). The reaction route is as follows:
Figure BDA0001504171930000021
in the process from the intermediate d to the intermediate f, a large amount of acid is consumed to remove the Boc protecting group, and then cyclization is carried out under alkaline conditions, acid-base neutralization is carried out in the process, and a large amount of gas is generated while violent heat is released, so that the operation is troublesome. When the chloro intermediate d is subjected to cyclization, the system is relatively complex, a large amount of byproducts are generated, and the reaction yield is relatively low.
CN143328476A discloses a preparation method of an intermediate compound (p), which comprises the steps of taking (S) -1- (benzyloxycarbonyl) -5-oxopyrrolidine-2-carboxylic acid (h) as a starting material, and carrying out eight-step reaction to obtain the compound (p). The reaction route is as follows:
Figure BDA0001504171930000022
the method has long route and low overall yield, and different protecting groups are required to be alternately used. In the method, expensive noble metal iridium is needed when the intermediate j is cyclized to generate the intermediate k, which is not beneficial to industrial scale-up production; the synthesis of the intermediate o from the intermediate n needs to be carried out under low temperature conditions, which is not beneficial to industrial production operation.
Disclosure of Invention
One object of the invention is to provide a method for preparing an abamectin intermediate compound of formula (I).
In order to achieve the purpose, the invention provides the following technical scheme:
a process for the preparation of a compound of formula (I) comprising the steps of:
1) preparing a compound of formula (III) from a compound of formula (II);
2) preparing a compound of formula (IV) from a compound of formula (III);
3) preparing a compound of formula (I) from a compound of formula (IV);
the reaction route is as follows:
Figure BDA0001504171930000031
wherein P is1Representing a protective group for a carboxylic acid function, P2Represents a protecting group for a hydroxylamine function, P3Represents a protecting group for an amine group.
In one embodiment, the protecting group P for a carboxylic acid functional group1Can be selected from alkyl, allyl, benzyl or P-nitrobenzyl, preferably P1Is benzyl (Bn). Protecting group P for hydroxylamine2May be selected from benzyl or allyl, preferably P2Is benzyl (Bn). Protecting group P for amino group3Can be selected from tert-butoxycarbonyl (Boc) or benzyloxycarbonyl (Cbz), preferably, P3Is tert-butoxycarbonyl (Boc).
In one embodiment, the compound of formula (II) in step 1) may be obtained starting from protected (S) -pyroglutamic acid of formula (a):
Figure BDA0001504171930000032
wherein P is1And P3As previously defined.
For example, the compound of formula (A) may be ring-opened by the action of trimethylsulfoxonium iodide and a base to provide a β -ketosulfoxonium compound of formula (II). The base may be potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium hydride or the like. The reaction solvent may be tetrahydrofuran, DMSO, N-dimethylformamide, ethyl acetate, dichloromethane, etc.
In one embodiment, the compound of formula (II) in step 1) is reacted with a hydrobromide salt of a hydroxylamine derivative to provide the compound of formula (III). For example, the hydroxylamine derivative may be a hydrobromide salt of benzyloxyamine (benzylhydroxylamine). The reaction solvent may be ethyl acetate, dichloromethane, tetrahydrofuran, DMSO, N-dimethylformamide, acetonitrile, or the like.
In one embodiment, the compound of formula (II) is treated with HBr-generating reagents in step 1) to provide a compound of formula (VI); reacting the compound of formula (VI) with a hydroxylamine derivative to obtain a compound of formula (III); preferably, the resulting compound of formula (VI) is reacted with the hydroxylamine derivative without isolation.
Figure BDA0001504171930000033
In one embodiment, the compound of formula (III) in step 2) is cyclized under the action of a base to give the compound of formula (IV). The alkali can be potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium hydride and the like; the reaction solvent may be tetrahydrofuran, ethyl acetate, dichloromethane, DMSO, N-dimethylformamide, acetonitrile, or the like.
In one embodiment, the compound of formula (IV) in step 2) reduces the oxime functional group and removes the amine protecting group in the presence of a reducing agent to provide the compound of formula (I). The reducing agent may be an alkali metal borohydride, such as sodium propionyl borohydride, sodium acetyl borohydride, sodium cyanoborohydride, sodium borohydride, lithium borohydride, potassium borohydride, and the like; the acid may be sulfuric acid, hydrochloric acid, acetic acid, trifluoroacetic acid, methanesulfonic acid, or the like.
In one embodiment, the method may further comprise reacting the compound of formula (I) with an acid to form a salt. The acid may be a salt formed from various inorganic acids, such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid or phosphoric acid, or an organic acid, such as formic acid, acetic acid, trifluoroacetic acid, propionic acid, benzoic acid, maleic acid, fumaric acid, succinic acid, tartaric acid, citric acid, oxalic acid, glyoxylic acid, aspartic acid, alkylsulfonic acids such as methanesulfonic acid and ethanesulfonic acid, arylsulfonic acids such as benzenesulfonic acid and p-toluenesulfonic acid. Preferably, the acid is oxalic acid and the salt of the compound of formula (I) is an oxalate salt.
In one exemplary embodiment, the method of making an abamectin intermediate compound of formula (I) comprises the steps of:
i) the N-Boc-L-pyroglutamic acid benzyl ester is subjected to ring-opening reaction under the action of trimethyl sulfoxide iodide and alkali to obtain a compound shown in a formula (II); the base can be potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium hydride and the like; the reaction solvent can be tetrahydrofuran, DMSO, N-dimethylformamide, ethyl acetate, dichloromethane and the like; the reaction temperature is-10 ℃ to 40 ℃;
II) reacting the compound of formula (II) with benzyloxyamine hydrobromide to give a compound of formula (III); the reaction solvent can be ethyl acetate, dichloromethane, tetrahydrofuran, DMSO, N-dimethylformamide, acetonitrile and the like, and the reaction temperature is 0-100 ℃;
III) carrying out cyclization reaction on the compound of the formula (III) under the action of alkali to obtain a compound of a formula (IV); the base can be potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium hydride and the like; the reaction solvent can be tetrahydrofuran, ethyl acetate, dichloromethane, DMSO, N-dimethylformamide, acetonitrile and the like; the reaction temperature is-30-50 ℃, and the preferable temperature is 0-30 ℃;
IV) reducing the oxime functional group of the compound of formula (IV) in the presence of a reducing agent and removing the amino protecting group in the presence of an acid to obtain a compound of formula (I); the reducing agent may be an alkali metal borohydride, such as sodium propionyl borohydride, sodium acetyl borohydride, sodium cyanoborohydride, sodium borohydride, lithium borohydride, potassium borohydride, and the like; the acid may be sulfuric acid, hydrochloric acid, acetic acid, trifluoroacetic acid, methanesulfonic acid, etc.; the reaction temperature is-30-40 ℃.
According to the needs, each step in any method of the invention can be carried out by steps, or can be carried out by a plurality of steps in a one-pot method, and all the steps can be used for obtaining the required products.
The present invention also provides compounds of formula (III):
Figure BDA0001504171930000041
wherein P is1、P2And P3As previously defined.
The invention also provides application of the compound shown in the formula (III) in preparing the avibactam intermediate shown in the formula (I).
The present invention also provides compounds of formula (IV):
Figure BDA0001504171930000051
wherein P is1、P2And P3As previously defined.
The method of the invention has the following beneficial effects:
1) the invention adopts brominated intermediate III which can be prepared by one-step reaction of intermediate II, and the operation is simple;
2) the bromo intermediate III is cyclized to prepare the intermediate IV, the by-product is less, the yield is high, and the cyclization reaction is more favorable than that of the chloro intermediate d;
3) the intermediate IV is subjected to deprotection and reduction reaction to obtain a compound I, the stepwise operation is not needed, the operation is simplified, and the consumption of a large amount of acid and the generation of a large amount of gas are avoided;
4) the method has the advantages of short route, simple operation, high yield, selective synthesis of the intermediate compound shown in formula (I) with high optical purity, avoidance of use of a large amount of acid and expensive noble metal, environmental friendliness and suitability for industrial application.
Detailed Description
The present invention is described in further detail below by way of examples. It is to be understood that the examples are for illustrative purposes only and are not intended to limit the scope of the present invention.
EXAMPLE 1 Benzyloxyamine hydrobromide
Figure BDA0001504171930000052
Benzyloxyamine hydrochloride (30g, 1.0eq) and sodium carbonate (20g, 1.0eq) were added to a mixed solvent of water (300mL) and ethyl acetate (300mL) in this order at room temperature, and stirred for 0.5 h. The organic phase was separated and the aqueous phase was extracted with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The concentrated residue was dissolved in tetrahydrofuran (600mL), hydrobromic acid (20mL) was added dropwise, and stirring was continued for 0.5h after the addition was complete. Concentration under reduced pressure, multiple stripping of water from the system with toluene and filtration gave 36.7g of a grey solid in 95% yield.
Example 2(S) -5-t-Butyloxycarbonylamino-6-benzyloxy-2, 6-dioxohexylenedisulfoxonium (II)
Figure BDA0001504171930000061
Potassium tert-butoxide (11.8g, 1.1eq) was added to a solution of trimethyl sulfoxide iodide (26.0g,1.25eq) in tetrahydrofuran (100mL) and DMSO (150mL) at room temperature, stirred at room temperature for 1h and then cooled to-10 ℃. To the reaction solution was added dropwise a solution of benzyl N-Boc-L-pyroglutamate (compound SM, 30.2g, 1.0eq) in tetrahydrofuran (60mL), and after completion of the dropwise addition, stirring was continued at-10 ℃. After TLC detection reaction, the reaction solution slowly raised to room temperature, added with 20% ammonium chloride aqueous solution (82mL) to quench the reaction, extracted with ethyl acetate three times, combined organic phase and 10% NaCl aqueous solution washing, anhydrous sodium sulfate drying, filtration, concentration, light yellow oily matter 40g, yield 100%.
Example 3(S) -5-Benzyloxyiimino-2-tert-butyloxycarbonylamino-6-bromo-hexanoic acid benzyl ester (III)
Figure BDA0001504171930000062
Compound II (17.5g, 1.0eq) obtained in example 2 was dissolved in ethyl acetate (135mL) at room temperature, benzyloxyamine hydrobromide (8.7g, 1.0eq) was added, and the reaction was stirred at 60 ℃. After the reaction, the reaction mixture was cooled to room temperature, washed with water, 1N aqueous hydrochloric acid solution and saturated aqueous NaCl solution in this order, dried over anhydrous sodium sulfate, filtered and concentrated to obtain 17.8g of pale yellow oily substance with a yield of 80%.
HRMS[M+H]519.1491. cis and trans configuration:1H NMR(400MHz,DMSO-d6)δ7.47-7.28(m,10H),5.18-5.05(m,4H),4.25-4.09(m,2H),4.06-3.85(m,1H),2.50-2.36(m,2H),2.09-1.94(m,1H),1.85(m,1H),1.38(s,9H).1H NMR(400MHz,DMSO-d6)δ7.41-7.27(m,10H),5.20-5.05(m,4H),4.14-3.83(m,3H),2.36(t,J＝7.8Hz,2H),2.01-1.88(m,1H),1.82(m,J＝16.8,1H),1.37(s,9H).
example 4(S) -5-benzyloxyimino-2-tert-butyloxycarbonylamino-6-bromo-hexanoic acid benzyl ester (III)
Figure BDA0001504171930000063
Methanesulfonic acid (2.93g,1.1eq) was slowly added to a solution of compound II (11.4g, 1.0eq) obtained in example 2 and lithium bromide (2.7g, 1.1eq) in tetrahydrofuran (50mL) at room temperature, and reacted at 50 ℃ for 5 hours. The reaction mixture was cooled to room temperature, and benzyloxyamine hydrochloride (4.6g,1.05eq) and sodium acetate (3.0g, 1.3eq), ethyl acetate (15mL) and water (15mL) were added thereto, and the mixture was stirred at room temperature. After the reaction is finished, an organic phase is separated, an aqueous phase is extracted twice by ethyl acetate, the organic phases are combined, washed by saturated saline solution, dried by anhydrous sodium sulfate, filtered, concentrated and purified by column chromatography to obtain a light yellow oily substance of 8.6g with the yield of 60 percent.
Example 5(S) -5-Benzyloxyiimino-1-tert-butyloxycarbonyl-piperidine-2-carboxylic acid benzyl ester (IV)
Figure BDA0001504171930000071
The oily compound III (17.8g, 1.0eq) obtained in example 3 was dissolved in tetrahydrofuran (180mL), cooled to 0 ℃ and potassium tert-butoxide (4.2g,1.1eq) was added, and the reaction was continued at 0 ℃ after the addition. After TLC monitoring reaction, adding saturated ammonium chloride to quench reaction, extracting three times with ethyl acetate, combining organic phases, drying with anhydrous sodium sulfate, filtering, concentrating to obtain light yellow oily matter, and directly carrying out next reaction. HRMS [ M + H ] M/Z:439.2251.
Example 6(S) -5-Benzyloxyiimino-1-tert-butyloxycarbonyl-piperidine-2-carboxylic acid benzyl ester (IV)
Figure BDA0001504171930000072
Compound II (8.1g, 1.0eq) obtained in example 2 was dissolved in ethyl acetate (50mL) at room temperature, benzyloxyamine hydrochloride (2.51g, 1.0eq) was added, and the reaction was stirred at 60 ℃. After the reaction is finished, the reaction liquid is cooled to room temperature, washed by water, 1N hydrochloric acid aqueous solution and saturated NaCl aqueous solution in sequence, dried by anhydrous sodium sulfate, filtered and concentrated to obtain light yellow oily matter, and the next reaction is directly carried out.
The resulting oil was dissolved in tetrahydrofuran (40mL), cooled to 0 deg.C, and potassium tert-butoxide (1.94g,1.1eq) was added, after which the reaction was continued at 0 deg.C. After TLC monitoring reaction, adding saturated ammonium chloride to quench reaction, extracting three times with ethyl acetate, combining organic phases, drying with anhydrous sodium sulfate, filtering, concentrating, purifying with silica gel column chromatography to obtain light yellow oily matter 1.65 g. The total yield of the two steps is 24%.
Example 7 benzyl (2S,5R) -5-benzyloxyaminopiperidine-2-carboxylate (I), oxalate salt
Figure BDA0001504171930000073
At room temperature, sodium borohydride (3.22g,2.5eq) was added to ethyl acetate (80mL) and cooled to 3 deg.C, propionic acid (18.9g,7.5eq) was added dropwise, and stirring was continued overnight after the addition was complete to give a solution of propionyl sodium borohydride in ethyl acetate. The pale yellow oil IV obtained in example 5 was dissolved in ethyl acetate (80mL), cooled to-20 deg.C, concentrated sulfuric acid (20.9g,6.25eq) was added, and the above solution of sodium propionylborohydride in ethyl acetate was added dropwise, maintaining the temperature at-20 deg.C. After the addition, the mixture is continuously stirred at the temperature of minus 20 ℃ until the reaction is finished. Adding strong ammonia water to quench the reaction, and separating an organic phase; the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated to give a red oil. The oil was dissolved in ethyl acetate (54mL) and heated to 45 ℃. And (3) dropwise adding an isopropanol (54mL) solution of oxalic acid (4.3g,1.0eq), adding methanol (108mL) after the addition is finished, continuously stirring for 15min, cooling for crystallization, and filtering to obtain 14g of white solid which is a mixture of (2S,5R) isomers (2S,5S) approximately equal to 1: 4. The mixture was recrystallized from methanol to give 2.5g of optically pure benzyl (2S,5R) -5-benzyloxyaminopiperidine-2-carboxylate oxalate. The total yield of the two steps is 14%.
Example 8 benzyl (2S,5R) -5-benzyloxyaminopiperidine-2-carboxylate (I), oxalate salt
Figure BDA0001504171930000081
At room temperature, sodium borohydride (3.22g,2.5eq) was added to ethyl acetate (80mL) and cooled to 3 ℃. Propionic acid (18.9g,7.5eq) was added dropwise to the system. Stirring the mixture overnight after the addition is finished to prepare propionyl sodium borohydride ethyl acetate solution. The pale yellow oil IV prepared according to example 5 was dissolved in ethyl acetate (80mL), concentrated sulfuric acid (20.9g,6.25eq) was added, stirred at room temperature for 2h and then cooled to-20 ℃ and the above ethyl propionyl borohydride solution was added dropwise, maintaining the temperature at-20 ℃. After the addition, the mixture is continuously stirred at the temperature of minus 20 ℃ until the reaction is finished. Adding strong ammonia water to quench the reaction, and separating an organic phase; the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined and washed with saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated to give a red oil. The oil was dissolved in ethyl acetate (54mL) and heated to 45 ℃. And (3) dropwise adding an isopropanol (54mL) solution of oxalic acid (4.3g,1.0eq), adding methanol (108mL) after the addition is finished, continuously stirring for 15min, cooling, crystallizing and filtering to obtain 12.4g of white solid, wherein the total yield of the two steps is 70%.
Example 9 benzyl (2S,5R) -5-benzyloxyaminopiperidine-2-carboxylate (I), oxalate salt
Figure BDA0001504171930000082
At room temperature, sodium borohydride (3.22g,2.5eq) was added to ethyl acetate (80mL) and cooled to 0 ℃. Acetic acid (15.3g,7.5eq) was added dropwise to the system. Stirring is continued overnight after the addition is finished, and the solution of sodium acetylborohydride and ethyl acetate is prepared. The pale yellow oil IV prepared according to the method of example 5 was dissolved in ethyl acetate (80mL), concentrated sulfuric acid (20.9g,6.25eq) was added, stirred at room temperature for 2h and then cooled to-20 ℃, and then the above-mentioned ethyl acetylborohydride solution was added dropwise, maintaining the temperature at-20 ℃. After the addition, the mixture is continuously stirred at the temperature of minus 20 ℃ until the reaction is finished. Adding strong ammonia water to quench the reaction, and separating an organic phase; the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined and washed with saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated to give a red oil. The oil was dissolved in ethyl acetate (54mL) and heated to 45 ℃. And (3) dropwise adding an isopropanol (54mL) solution of oxalic acid (4.3g,1.0eq), adding methanol (108mL) after the addition is finished, continuously stirring for 15min, cooling for crystallization, and filtering to obtain 4.6g of a white solid which is a mixture of (2S,5R) isomers (2S,5S) approximately equal to 1:4, wherein the total yield of the two steps is 26%.
Example 10 benzyl (2S,5R) -5-benzyloxyaminopiperidine-2-carboxylate (I), oxalate salt
Figure BDA0001504171930000091
The pale yellow oil IV prepared as in example 5 was dissolved in ethyl acetate (80mL), concentrated sulfuric acid (20.9g,6.25eq) was added, stirred at room temperature for 2h and then cooled to-20 deg.C, and sodium cyanoborohydride (4.3g,2.0eq) was added to the reaction maintaining the temperature at-20 deg.C. After the addition, the mixture is continuously stirred at the temperature of minus 20 ℃ until the reaction is finished. Adding strong ammonia water to quench the reaction, and separating an organic phase; the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined and washed with saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated to give a red oil. The oil was dissolved in ethyl acetate (54mL) and heated to 45 ℃. And (3) dropwise adding an isopropanol (54mL) solution of oxalic acid (4.3g,1.0eq), adding methanol (108mL) after the addition is finished, continuously stirring for 15min, cooling, crystallizing and filtering to obtain 8.9g of white solid, wherein the total yield of the two steps is 50%.
The outstanding contribution of the invention is firstly to provide a new synthetic route for preparing the key intermediate (I) of the abamectin, and the above is only an exemplary embodiment for explaining the invention. Based on the disclosure of the present invention, those skilled in the art can make various modifications and changes to the reaction conditions and post-treatment of each step, such as changing the feeding ratio of the reaction raw materials, changing the reaction temperature, using similar substitute reagents, etc., all falling within the protection scope of the present invention.

Claims (5)

1. A process for the preparation of a compound of formula (I) comprising the steps of:
1) preparing a compound of formula (III) from a compound of formula (II);
2) preparing a compound of formula (IV) from a compound of formula (III);
3) preparing a compound of formula (I) from a compound of formula (IV);
the reaction route is as follows:
Figure FDA0002949819160000011
II) reacting the compound of formula (II) with benzyloxyamine hydrobromide to give a compound of formula (III); the reaction solvent is selected from ethyl acetate, dichloromethane, tetrahydrofuran, DMSO, N-dimethylformamide and acetonitrile, and the reaction temperature is 0-100 ℃;
III) carrying out cyclization reaction on the compound of the formula (III) under the action of alkali to obtain a compound of a formula (IV); the alkali is selected from potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide and sodium hydride; the reaction solvent is selected from tetrahydrofuran, ethyl acetate, dichloromethane, DMSO, N-dimethylformamide and acetonitrile; the reaction temperature is-30 ℃ to 50 ℃;
IV) reducing the oxime functional group and removing the amine protecting group of the compound of formula (IV) in the presence of a reducing agent and an acid to obtain a compound of formula (I); the reducing agent is selected from sodium propionyl borohydride and sodium acetyl borohydride; the acid is selected from sulfuric acid, hydrochloric acid, trifluoroacetic acid and methanesulfonic acid; the reaction temperature is-30-40 ℃.
2. The process of claim 1, wherein the reaction temperature of step 2) is from 0 ℃ to 30 ℃.
3. The process of claim 1, further comprising reacting the compound of formula (I) with an acid to form a salt.
4. The process according to claim 1, wherein the compound of formula (II) is prepared by ring opening of a compound of formula (a) under the action of trimethyl sulphoxide iodide and a base:
Figure FDA0002949819160000012
5. the method of claim 4, comprising the steps of:
i) the N-Boc-L-pyroglutamic acid benzyl ester is subjected to ring-opening reaction under the action of trimethyl sulfoxide iodide and alkali to obtain a compound shown in a formula (II); the alkali is selected from potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide and sodium hydride; the reaction solvent is selected from tetrahydrofuran, DMSO, N-dimethylformamide, ethyl acetate and dichloromethane; the reaction temperature is-10-40 ℃.
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