阅读说明：本技术 吡咯啉酮类化合物及其合成方法 (Pyrrolinone compound and synthetic method thereof ) 是由 陈发普 石聿新 陈发凯 于 2020-12-22 设计创作，主要内容包括：本发明提供了一种吡咯啉酮类化合物,其结构式如式1所示,其中,R-1选自C-1～C-5烷氧基、苄氧基、C-1～C-5烷基和苯基中的一种；R-2,R-3分别独立地选自氢、C-1～C-5烷基、C-1～C5烷氧基、C-1～C-5烷硫基、C-1～C-5烷亚磺酰基、C-1～C-5烷磺酰基、不同取代的苯基、不同取代的苯氧基、不同取代的苯硫基、不同取代的苯亚磺酰基和不同取代的苯磺酰基中的一种；n-1,n-2取自1～5的整数。其可以作为药物中间体。本发明还提供了该吡咯啉酮类化合物的合成方法,其更适合工业化,成本更低,合成条件更温和。(The invention provides a pyrrolinone compound, the structural formula of which is shown as formula 1, wherein R is 1 Is selected from C 1 ～C 5 Alkoxy, benzyloxy, C 1 ～C 5 One of an alkyl group and a phenyl group; r 2 ，R 3 Each independently selected from hydrogen and C 1 ～C 5 Alkyl radical, C 1 C5 alkoxy, C 1 ～C 5 Alkylthio radical, C 1 ～C 5 Alkylsulfinyl radical, C 1 ～C 5 One of an alkylsulfonyl group, a differently substituted phenyl group, a differently substituted phenoxy group, a differently substituted phenylthio group, a differently substituted phenylsulfinyl group, and a differently substituted phenylsulfonyl group; n is 1 ,n 2 An integer from 1 to 5. It can be used as pharmaceutical intermediate. The invention also provides a synthesis method of the pyrrolinone compound, which is more suitable for industrialization, has lower cost and milder synthesis conditions。)

1. A pyrrolinone compound is characterized in that the structural formula is shown as formula 1,

wherein R is₁Is selected from C₁～C₅Alkoxy, benzyloxy, C₁～C₅One of an alkyl group and a phenyl group; r₂，R₃Each independently selected from hydrogen and C₁～C₅Alkyl radical, C₁C5 alkoxy, C₁～C₅Alkylthio radical, C₁～C₅Alkylsulfinyl radical, C₁～C₅One of an alkylsulfonyl group, a differently substituted phenyl group, a differently substituted phenoxy group, a differently substituted phenylthio group, a differently substituted phenylsulfinyl group, and a differently substituted phenylsulfonyl group; n is₁,n₂An integer from 1 to 5.

2. The pyrrolinone compound of claim 1, wherein R is₃Is hydrogen, n₁Is 1.

3. Pyrrolinones according to claim 2, characterized in that n is₂Is 2.

4. The pyrrolinone compound of claim 3, having a structural formula selected from one of the following structural formulae:

5. a method for preparing pyrrolinones compound according to claim 1, which is prepared by reacting a compound represented by formula 6, wherein the reaction formula is as follows:

6. the method for preparing pyrrolinones according to claim 5, wherein the pyrrolinones are prepared by the base catalysis of the compound of formula 6 in a solvent.

7. The method according to claim 6, wherein the solvent used in the step of preparing the compound of formula 1 from the compound of formula 6 is one or more selected from tetrahydrofuran, methanol, ethanol, water, acetone, DMF and DMSO, and the base is one or more selected from sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium tert-butoxide, DBU and dimethylaminopyridine.

8. The method for preparing pyrrolinones according to claim 5, wherein the compound represented by formula 6 is prepared by reacting a compound represented by formula 5, wherein the reaction formula is as follows:

wherein R is₁Is selected from C₁～C₅Alkoxy, benzyloxy, C₁～C₅One of an alkyl group and a phenyl group; r₂，R₃Each independently selected from hydrogen and C₁～C₅Alkyl radical, C₁～C₅Alkoxy radical, C₁～C₅Alkylthio radical, C₁～C₅Alkylsulfinyl radical, C₁～C₅Alkylsulfonyl, differently substituted phenyl, differentlyOne of a substituted phenoxy group, a differently substituted phenylthio group, a differently substituted phenylsulfinyl group, and a differently substituted phenylsulfonyl group; n is₁,n₂An integer from 1 to 5.

9. The method according to claim 8, wherein the compound of formula 5 is reacted with an acid anhydride or acid chloride in a solvent under base catalysis to produce the compound of formula 6.

10. The method for preparing pyrrolinones according to claim 9, wherein in the step of reacting the compound represented by formula 5 with an acid anhydride or an acid chloride to produce the compound represented by formula 6 in a solvent under the catalysis of a base, the base is selected from one or more of triethylamine, pyridine, dimethylaminopyridine, diisopropylethylamine, sodium carbonate, potassium carbonate and sodium bicarbonate; the solvent is selected from one or more of dichloromethane, chloroform, tetrahydrofuran, acetone and ethyl acetate.

11. The method for preparing pyrrolinones compound according to claim 9, wherein in the step of reacting the compound shown in formula 5 with acid anhydride or acid chloride in a solvent under base catalysis to obtain the compound shown in formula 6, the molar ratio of the compound shown in formula 5, the acid chloride or the acid anhydride and the base is 1 (0.8-2): (0.8-2).

12. The method for preparing pyrrolinones compound according to claim 8, wherein the reaction temperature is controlled to be 0-40 ℃ in the step of preparing the compound represented by formula 6 from the compound represented by formula 5.

13. The method for preparing pyrrolinones according to claim 8, wherein the compound represented by formula 5 is prepared by reacting a compound represented by formula 4, wherein the reaction formula is as follows:

14. the method for producing pyrrolinones according to claim 13, wherein the compound of formula 4 is deprotected in a solvent under acidic conditions to produce a compound of formula 5.

15. The method for preparing pyrrolinones according to claim 14, wherein the acidity regulator used in the step of preparing the compound of formula 5 from the compound of formula 4 is one or more selected from the group consisting of hydrochloric acid, sulfuric acid, formic acid and acetic acid; the solvent used is selected from one or more of dichloromethane, chloroform, tetrahydrofuran, acetone and ethyl acetate.

16. The method for preparing pyrrolinones according to claim 15, wherein the molar ratio of the compound of formula 4 to the acid in the preparation of the compound of formula 5 from the compound of formula 4 is 1 (0.1-1).

17. The method for preparing pyrrolinones compound according to claim 13, wherein the reaction temperature is controlled to be 20-30 ℃ during the preparation of the compound of formula 5 from the compound of formula 4.

18. The method for preparing pyrrolinones according to claim 13, wherein the compound represented by formula 4 is prepared by reacting a compound represented by formula 2 with a compound represented by formula 3, and the reaction formula is as follows:

19. the method for preparing pyrrolinones according to claim 18, wherein the compound of formula 2 and the compound of formula 3 are reacted in a solvent under base catalysis to form the compound of formula 4.

20. The method for preparing pyrrolinones according to claim 19, wherein the compound of formula 2 or 3 is prepared by using one or more solvents selected from dichloromethane, chloroform, tetrahydrofuran, acetone and ethyl acetate, and the base is one or more bases selected from triethylamine, pyridine, dimethylaminopyridine, diisopropylethylamine, sodium carbonate, potassium carbonate and sodium bicarbonate.

21. The method for preparing pyrrolinones according to claim 19, wherein in the step of preparing the compound represented by formula 4 from the compound represented by formula 2 and the compound represented by formula 3, the molar ratio of the compound represented by formula 2 to the compound represented by formula 3 to the base used is 1 (0.8-2): (0.8-2).

22. The method for preparing pyrrolinones compound according to claim 18, wherein the reaction temperature in the step of preparing the compound represented by formula 4 from the compound represented by formula 2 and the compound represented by formula 3 is controlled to be 15-30 ℃.

Technical Field

The invention belongs to the field of drug synthesis, and particularly relates to a pyrrolinone compound and a synthesis method thereof.

Background

Pyrrolinone is an important structural fragment of medicaments and food additives such as glimepiride, bilirubin, biliverdin, phycocyanin and the like.

For the synthesis of such compounds there are generally several methods:

1) p-toluenesulfonylpyrrole method:

the method (Monatsh. chem.,2014,145,5,775-789) takes p-toluenesulfonyl pyrrole as a raw material, and the pyrrolinone compound is obtained through the steps of bromination, hydrolysis, reduction and the like, a large amount of trifluoroacetic acid is used in the hydrolysis process, the pollution is great, sodium borohydride is used for reduction, and the cost is higher.

2) Pyrrole amide method:

the method (J.org.chem.2006,71, 6678-Bus6681) uses pyrrole amide as raw material, and generates pyrrole aldehyde by reduction of lithium aluminum hydride, and then generates pyrrolinone by oxidation and hydrogen oxidation.

3) Ethyl acetoacetate process

The method (Tetrahedron Lett.,2003,44, 4853-one 4855) uses ethyl acetoacetate as a starting material, and obtains the pyrrolinone compound through sodium cyanide addition, catalytic hydrogenation and hydrolysis. The raw material sodium cyanide used in the method is a highly toxic raw material, catalytic hydrogenation needs to be carried out under high pressure, the yield is only 15%, and the requirement of industrial production is also limited.

4) The method takes allylamine as a starting material:

compared with the method, the method (Synthesis, 2015, 47, 955-. Sodium borohydride and expensive palladium chloride are still used.

Therefore, it is necessary to develop a synthetic method of pyrrolinone compound, which is more suitable for industrialization, has lower cost and milder synthetic conditions.

Disclosure of Invention

The invention aims to solve at least one technical problem in the prior art to a certain extent, and therefore provides a pyrrolinone compound, the structural formula of which is shown as formula 1,

wherein R is₁Is selected from C₁～C₅Alkoxy, benzyloxy, C₁～C₅One of an alkyl group and a phenyl group; r₂，R₃Each independently selected from hydrogen and C₁～C₅Alkyl radical, C₁～C₅Alkoxy radical, C₁～C₅Alkylthio radical, C₁～C₅Alkylsulfinyl radical, C₁～C₅One of an alkylsulfonyl group, a differently substituted phenyl group, a differently substituted phenoxy group, a differently substituted phenylthio group, a differently substituted phenylsulfinyl group, and a differently substituted phenylsulfonyl group; n is₁,n₂An integer from 1 to 5. The different substitution includes substitution at different positions, such as meta-substitution, ortho-substitution, para-substitution, and further includes substitution at different substituents, such as C₁～C₅Alkyl substituted, haloAnd (4) substitution of elements.

In the technical scheme of the invention, R₃Is hydrogen, n₁Is 1.

In the technical scheme of the invention, n₂Is 2.

In the technical scheme of the invention, the structural formula of the pyrrolinone compound is selected from one of the following structural formulas:

the invention also provides a preparation method of the pyrrolinone compound, which is prepared by reacting the compound shown in the formula 6, wherein the reaction formula is shown as follows:

in the technical scheme of the invention, the compound is prepared from the compound shown in the formula 6 in a solvent through base catalysis.

In the technical scheme of the invention, in the step of preparing the compound of formula 1 from the compound of formula 6, the solvent used is one or more selected from tetrahydrofuran, methanol, ethanol, water, acetone, DMF and DMSO, and the base is one or more selected from sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium tert-butoxide, DBU and dimethylaminopyridine.

In the technical scheme of the invention, the compound shown in the formula 6 is prepared by reacting the compound shown in the formula 5, wherein the reaction formula is as follows:

wherein R is₁Is selected from C₁～C₅Alkoxy, benzyloxy, C₁～C₅One of an alkyl group and a phenyl group; r₂，R₃Each independently selected from hydrogen and C₁～C₅Alkyl radical, C₁～C₅Alkoxy radical, C₁～C₅Alkylthio radical, C₁～C₅Alkylsulfinyl radical, C₁～C₅One of an alkylsulfonyl group, a differently substituted phenyl group, a differently substituted phenoxy group, a differently substituted phenylthio group, a differently substituted phenylsulfinyl group, and a differently substituted phenylsulfonyl group; n is₁,n₂An integer from 1 to 5. The different substitution includes substitution at different positions, such as meta-substitution, ortho-substitution, para-substitution, and further includes substitution at different substituents, such as C₁～C₅Alkyl substitution, halogen substitution.

In the technical scheme of the invention, the compound shown in the formula 5 reacts with acid anhydride or acyl chloride in a solvent through base catalysis to generate the compound shown in the formula 6.

In the technical scheme of the invention, in the step of generating the compound shown in the formula 6 by the reaction of the compound shown in the formula 5 and acid anhydride or acyl chloride in a solvent through base catalysis, the base is selected from one or more of triethylamine, pyridine, dimethylaminopyridine, diisopropylethylamine, sodium carbonate, potassium carbonate and sodium bicarbonate; the solvent is selected from one or more of dichloromethane, chloroform, tetrahydrofuran, acetone and ethyl acetate.

In the technical scheme of the invention, in the step of generating the compound shown in the formula 6 by the reaction of the compound shown in the formula 5 and acid anhydride or acyl chloride in a solvent through base catalysis, the molar ratio of the compound shown in the formula 5 to the acid chloride or the acid anhydride to the base is 1 (0.8-2): (0.8-2).

In the technical scheme of the invention, in the step of generating the compound shown in the formula 6 by reacting the compound shown in the formula 5 with acid anhydride or acyl chloride in a solvent under the catalysis of alkali, the reaction temperature is controlled to be 0-30 ℃.

In the technical scheme of the invention, the compound shown in the formula 5 is prepared by reacting the compound shown in the formula 4, wherein the reaction formula is as follows:

in the technical scheme of the invention, the compound of formula 4 is deprotected in a solvent under an acidic condition to generate a compound of formula 5.

In the technical scheme of the invention, in the step of preparing the compound of formula 5 from the compound of formula 4, the acid regulator used is one or more selected from hydrochloric acid, sulfuric acid, formic acid and acetic acid; the solvent used is selected from one or more of dichloromethane, chloroform, tetrahydrofuran, acetone and ethyl acetate.

In the technical scheme of the invention, in the process of preparing the compound shown in the formula 5 from the compound shown in the formula 4, the molar ratio of the compound shown in the formula 4 to the acid is 1 (0.1-1).

In the technical scheme of the invention, in the process of preparing the compound shown in the formula 5 from the compound shown in the formula 4, the reaction temperature is controlled to be 20-30 ℃.

In the technical scheme of the invention, the compound shown in the formula 4 is prepared by reacting a compound shown in the formula 2 with a compound shown in the formula 3, wherein the reaction formula is as follows:

in the technical scheme of the invention, the compound of formula 2 and the compound of formula 3 react in a solvent under the catalysis of a base to generate the compound of formula 4.

In the technical scheme of the invention, in the step of preparing the compound shown in formula 4 from the compound shown in formula 2 and the compound shown in formula 3, the solvent used is one or more selected from dichloromethane, chloroform, tetrahydrofuran, acetone and ethyl acetate, and the base used is one or more selected from triethylamine, pyridine, dimethylaminopyridine, diisopropylethylamine, sodium carbonate, potassium carbonate and sodium bicarbonate.

In the technical scheme of the invention, in the step of preparing the compound shown in the formula 4 from the compound shown in the formula 2 and the compound shown in the formula 3, the molar ratio of the compound shown in the formula 2, the compound shown in the formula 3 and the used base is 1 (0.8-2): (0.8-2);

in the technical scheme of the invention, in the step of preparing the compound shown in the formula 4 from the compound shown in the formula 2 and the compound shown in the formula 3, the reaction temperature is controlled to be 15-30 ℃.

The invention has the beneficial effects that:

1. the novel pyrrolinone compound can be used as a drug intermediate, and has high yield and mild conditions for preparing the phycocyanin and the glimepiride.

2. The invention provides a novel synthesis method of pyrrolinone compounds, which is more suitable for industrialization, lower in cost and milder in synthesis conditions.

Detailed Description

The scheme of the invention will be explained with reference to the examples. It will be appreciated by those skilled in the art that the following examples are illustrative of the invention only and should not be taken as limiting the scope of the invention. The examples, where specific techniques or conditions are not indicated, are to be construed according to the techniques or conditions described in the literature in the art or according to the product specifications. NMR was measured using a Bruker-AMX400 NMR spectrometer; ESI-MS with Finnigan-MAT-95 mass spectrometer; all reagents were analytically pure (national reagents company); in the following examples, 2, 2-dimethoxypropylamine was prepared according to the method of the document eur.j.med.chem.,1995,30,931 to 942; the 4-p-toluenesulfonyl butyryl chloride is prepared according to the method of MedChemComm,2017,8, 1268-1274.

Example 1: compound 4 a: synthesis of N- (2, 2-dimethoxypropyl) -4-p-toluenesulfonyl butyramide

The preparation of compound 4a is as follows: weighing 6.80 g of compound 2, 2-dimethoxypropylamine (57.1mmol), dissolving with 20ml of dichloromethane, adding 6.10 g of triethylamine (60.4mmol), cooling to 0 ℃, slowly dropwise adding 13.03 g (57.1mmol) of 4-p-toluenesulfonyl butyryl chloride dissolved in 20ml of dichloromethane, controlling the temperature below 5 ℃, stirring for 10 hours at 20-30 ℃ after dropwise adding, filtering to obtain N- (2, 2-dimethoxypropyl) -4-p-toluenesulfonyl butyramide, washing a filter cake with dichloromethane, and directly using the filtrate for the next reaction.

Example 2: compound 4 b: synthesis of N- (2, 2-dimethoxypropyl) butanamide:

the preparation of compound 4b is as follows: weighing 2, 2-dimethoxypropylamine (55.8mmol), dissolving with 20ml of tetrahydrofuran, adding potassium carbonate (63.7mmol), cooling to 0 ℃, slowly dropwise adding 5.97g (55.8mmol) of butyryl chloride dissolved in 20ml of tetrahydrofuran, controlling the temperature below 5 ℃, stirring for 10 hours at 15-25 ℃ after dropwise adding is finished, filtering to obtain N- (2, 2-dimethoxypropyl) -4-p-tolylsulfanyl butyramide, washing a filter cake with dichloromethane, and directly using a filtrate for the next reaction.

Example 3: compound 5 a: synthesis of N-acetonyl-4-p-toluenesulfonyl butyramide

The preparation of compound 5a is as follows: to the dichloromethane solution containing the compound 4a obtained in example 1, 8.0 g (10.8mmol) of 5% diluted hydrochloric acid was added, stirred at 15 to 35 ℃ for 4 hours, and then allowed to stand to separate a dichloromethane layer, which was then washed with saturated brine, water, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 10.20 g of a white solid, i.e., N-acetonyl-4-p-tolylsulfanylbutanamide, with a two-step yield (total yield of two-step reactions of example 1 and example 3) of 96%. N-acetonyl-4-p-tolylsulfanylbutanamide:¹H NMR(400MHz,CDCl₃):δ1.92～1.97(m，2H)，2.20(s,3H),2.31(s,3H),2.39(t,6.8Hz，2H),2.93(t,J＝6.8Hz,2H),4.14(d,J＝4.0Hz,2H),6.22(s,1H),7.09(d,J＝4.0Hz,2H),7.26(d,J＝8.0Hz,2H)；ESI-Mass:266.0[M+H]⁺。

example 4: compound 5 b: synthesis of N-acetonyl-4-butanamide

Compound 5b was prepared as follows: to the dichloromethane solution containing the compound 4b obtained in example 2Adding 8.0 g of 5% dilute hydrochloric acid into the solution, stirring for 4 hours at 15-35 ℃, standing, separating dichloromethane layers, sequentially washing with saturated saline solution and water, drying with anhydrous sodium sulfate, filtering, and concentrating to obtain a white solid, namely N-acetonyl-4-butyramide, wherein the two-step yield (the total yield of the two-step reactions of the example 2 and the example 4) is 92%. N-acetonyl-4-butanamide¹H NMR(400MHz,CDCl₃):δ0.99(t，J＝7.0Hz，3H)，1.64～1.70(m,2H),2.21(s,3H),2.34(t,J＝6.8Hz,2H),4.16(s,2H)；ESI-Mass:144.18[M+H]⁺。

Example 5: compound 6 a: synthesis of N-acetonyl-N-tert-butyloxycarbonyl-4-p-toluenesulfonyl butanamide

The preparation of compound 6a is as follows: weighing 8 g of compound 5a, dissolving in 50 ml of dichloromethane, adding 8.0 g of DMAP, cooling to 0 ℃, and slowly dropwise adding 13.2 g of Boc dissolved in 90 ml of dichloromethane₂And O, controlling the temperature to be not more than 5 ℃, stirring for 10 hours at 15-30 ℃ after the addition is finished, pouring the reactant into 100 ml of ice water, acidifying the water phase to the pH value of 3 by using dilute hydrochloric acid, separating an organic layer, washing the organic layer by using saturated sodium bicarbonate and common salt water in sequence, drying the organic layer by using anhydrous sodium sulfate, filtering and concentrating to obtain light yellow liquid 10.81 g, namely N-acetonyl-N-tert-butoxycarbonyl-4-p-tolylsulfanyl butyramide, wherein the yield is 99%.¹H NMR(400MHz,CDCl₃):δ1.47(s，9H)，1.93～1.97(m，2H)，2.14(s,3H),2.30(s,3H),2.93(t,J＝6.0Hz,2H),3.08(t,J＝7.2Hz,2H),4.49(s,2H),7.08(d,J＝8.2Hz,2H),7.25(d,J＝8.2Hz,2H)；ESI-Mass:387.97[M+Na]⁺。

Example 6: compound 6 b: synthesis of N-acetonyl-N-tert-butyloxycarbonyl butanamide

Compound 6b was prepared as follows: 8 g of compound 5b are weighed out and dissolved in 50 mlDichloromethane, then 8.0 g of DMAP (dimethyl acetamide), cooling to 0 ℃, slowly dropwise adding 13.2 g of Boc2O dissolved in 90 ml of dichloromethane, controlling the temperature to be not more than 5 ℃, stirring for 10 hours at 15-35 ℃ after the addition is finished, pouring the reaction product into 100 ml of ice water, acidifying the water phase to the pH value of 3 by using dilute hydrochloric acid, separating an organic layer, sequentially washing by using saturated sodium bicarbonate and salt water, drying by using anhydrous sodium sulfate, filtering, and concentrating to obtain a pale yellow oily substance, namely N-acetonyl-N-tert-butoxycarbonylbutyramide, wherein the yield is 97%. N-acetonyl-N-tert-butoxycarbonylbutyramide:¹H NMR(400MHz,CDCl₃):δ1.00(t,J＝7.2Hz，3H),1.48(s,9H),1.76～1.78(m,2H),2.23(s,3H),2.95(m,2H),4.45(s,2H),ESI-Mass:244.22[M+H]⁺。

example 7: compound 1 a: synthesis of N-tert-butoxycarbonyl-3- (2-p-tolylsulfanylethyl) -4-methyl-1H-2 (5H) pyrrolidone

The preparation of compound 1a is as follows: weighing 6.80 g of compound 6a, adding 50 ml of DMSO (dimethylsulfoxide) dissolved with 3.0 g of sodium hydroxide, stirring at 15-35 ℃ for 30 minutes, pouring the reaction product into 100 ml of ice water, extracting with ethyl acetate, washing with dilute hydrochloric acid to neutrality, washing with saturated saline, drying with anhydrous sodium sulfate, filtering, concentrating, and recrystallizing with ethanol to obtain an earthy yellow solid 6.0 g, wherein the yield is 84%.¹H NMR(400MHz,CDCl₃):δ1.55(s，9H)，1.95(s，3H)，2.30(s,3H),2.57(t,J＝7.2Hz，2H),3.11(t,J＝7.2Hz,2H),4.03(s,2H),7.08(d,J＝8.0Hz,2H),7.25(d,J＝8.0Hz,2H)；ESI-Mass:717.14[2M+Na]⁺。

Example 8: compound 1 b: synthesis of N-tert-butyloxycarbonyl-3-ethyl-4-methyl-1H-2 (5H) pyrrolidone

The preparation of compound 1b is as follows: 6.80 g of Compound 6b are weighed in with 3.0 g of sodium hydroxide dissolvedAnd (2) adding 50 ml of DMSO, stirring at 15-35 ℃ for 30 minutes, pouring the reaction into 100 ml of ice water, extracting with ethyl acetate, washing with dilute hydrochloric acid to be neutral, washing with saturated saline solution, drying with anhydrous sodium sulfate, filtering, concentrating, and recrystallizing with ethanol to obtain the compound 1b N-tert-butoxycarbonyl-3-ethyl-4-methyl-1H-2 (5H) pyrrolidone as a colorless oily substance with the yield of 77%.¹H NMR(400MHz,CDCl₃):δ1.10(t,J＝7.0Hz,3H),1.49(s,9H),2.01(s,3H),2.32(q,J＝7.4Hz,2H),4.20(s,2H),ESI-Mass:226.22[M+1]⁺。

Example 9:

compound 1a was used for the synthesis of phycocyanin intermediates:

3.47 g of the compound of the formula 1a and 3.21 g of tert-butyl 5-formyl-4-methyl-3-allyloxycarbonylethyl-2-pyrrolidinoate were weighed, mixed and dissolved in 30ml of toluene, 5.0g of DBU was added thereto, the mixture was refluxed for 2 hours under heating, distilled under reduced pressure to remove the solvent, and the residue was recrystallized from 20ml of methanol to give 4.12 g of a yellow solid with a yield of 75%, the spectral data of which are Synlett 1999, S1,901-904.

Example 10:

compound 1b was used for the synthesis of glimepiride intermediates:

weighing 1.12 g of the compound shown in the formula 1b, dissolving the compound in 10 ml of ethyl acetate, cooling to 0 ℃, slowly adding 10 ml of 4N hydrochloric acid dissolved in 15 ml of dioxane, slowly raising the temperature to 15-35 ℃, then continuously stirring for 2 hours, extracting with ethyl acetate, washing with saturated saline, drying with anhydrous sodium sulfate, and carrying out column chromatography to obtain 0.46 g of a white solid with the yield of 75%. Spectrogram data identical to Synthesis, 2015; 47, 955-960.

Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention, and that variations, modifications, substitutions and alterations can be made to the above embodiments by those of ordinary skill in the art within the scope of the present invention.