A preparation method of 2-acyl-4-oxobutyrate derivatives

Abstract

The invention discloses a method for preparing a 2-acyl-4-oxobutyrate derivative, comprising the steps of: (1) mixing a β-carbonyl ester, a sulfonium ylide, a Lewis acid, and an organic solvent, and reacting the mixture at 85-95° C. for 20-25 hours under an air atmosphere; (2) diluting the material obtained in step (1) with ethyl acetate, and then washing with water to separate an organic phase; and (3) drying, filtering, concentrating, and chromatographically purifying the organic phase obtained in step (2) to obtain the 2-acyl-4-oxobutyrate derivative. The method has good chemical selectivity, readily available raw materials, high yield, mild reaction conditions, short reaction time, a wide substrate range, strong reaction specificity, and simple post-processing.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for preparing a 2-acyl-4-oxobutyrate derivative. Background Art

[0002] 2-Acyl-4-oxobutyrate derivatives are important carbonyl-containing compounds. Their substructure, 1,4-diketone compounds, are important organic synthesis intermediates, enabling the synthesis of numerous physiologically active five-membered heterocycles such as furans, thiophenes, and pyrroles. They are also crucial raw materials or precursors for the synthesis of cyclopentenone-type natural products and are widely used in pharmaceutical synthesis, combinatorial chemistry, materials science, and fine chemicals. Furthermore, the most common application of 1,4-diketone compounds in existing technologies is through the Paal-Knorr method. Therefore, the efficient synthesis and functionalization of 1,4-diketone compounds has been a hot topic of research both domestically and internationally. Summary of the Invention

[0003] The present invention aims to overcome the defects of the prior art and provide a method for preparing a 2-acyl-4-oxobutyrate derivative.

[0004] Reaction formula of the present invention is as follows:

[0005]

[0006] The technical solutions of the present invention are as follows:

[0007] A method for preparing a 2-acyl-4-oxobutyrate derivative comprises the following steps:

[0008] (1) mixing β-carbonyl ester, sulfonium ylide, Lewis acid and organic solvent, and reacting at 85-95° C. for 20-25 hours under air atmosphere;

[0009] (2) diluting the material obtained in step (1) with ethyl acetate, washing with water, and separating to obtain an organic phase;

[0010] (3) drying, filtering, concentrating and chromatographically purifying the organic phase obtained in step (2) to obtain the 2-acyl-4-oxobutyrate derivative;

[0011] The structural formula of the above-mentioned β-carbonyl ester is wherein R1 is hydrogen, alkoxy, alkyl, substituted or unsubstituted aromatic group, and the substituent on the substituted aromatic group is alkyl, alkoxy or halogen;

[0012] The structural formula of the above-mentioned sulfonium ylide is Wherein R2 is hydrogen, alkoxy, alkyl, alkenyl, substituted or unsubstituted aromatic group, and the substituent on the substituted aromatic group is alkyl, alkoxy or halogen.

[0013] In a preferred embodiment of the present invention, the halogen is fluorine, chlorine, bromine or iodine.

[0014] In a preferred embodiment of the present invention, the sulfonium ylide is 2-(dimethyl(oxo)-λ 6 -sulfonimide)-1-(4-methoxyphenyl)ethane-1-one, 2-(dimethyl(oxo)-λ 6 -sulfonimide)-1-phenylethane-1-one, 1-(4-bromophenyl)-2-(dimethyl(oxo)-λ 6 -sulfonimide)ethane-1-one, 2-(dimethyl(oxo)-λ 6 -sulfonimide)-1-(2-thienyl)ethane-1-one, 2-(dimethyl(oxo)-λ 6 -sulfonimide)-1-(2-phenoxyphenyl)ethane-1-one, (E)-1-(dimethyl(oxo)-λ 6 -sulfonimide)-4-phenylbut-3-en-2-one or 2-(dimethyl(oxo)-λ 6 -sulfonimide)propyl acetate.

[0015] In a preferred embodiment of the present invention, the Lewis acid is potassium bromide, lithium chloride, zinc chloride, aluminum chloride, potassium iodide, lithium iodide, ferric chloride or ferric bromide.

[0016] More preferably, the Lewis acid is lithium bromide.

[0017] In a preferred embodiment of the present invention, the organic solvent is N,N-dimethylformamide, N,N-dimethylacetamide, 1,2-dichloroethane, toluene, 1,4-dioxane, tetrahydrofuran, hexafluoroisopropanol, isopropanol or acetonitrile.

[0018] More preferably, the organic solvent is acetonitrile.

[0019] In a preferred embodiment of the present invention, the β-carbonyl ester is diethyl malonate, ethyl acetoacetate, methyl 3-oxo-3-(p-tolyl)propionate, methyl 3-oxo-3-(m-tolyl)propionate, methyl 3-(4-methoxyphenyl)-3-oxopropionate, methyl 3-(3-methoxyphenyl)-3-oxopropionate or methyl 3-(4-bromophenyl)-3-oxopropionate.

[0020] In a preferred embodiment of the present invention, the molar ratio of the β-carbonyl ester, the sulfonium ylide, and the Lewis acid is 1:1:1, and every 0.01 mmol of ethyl benzimide or its derivative corresponds to 0.1 mL of the organic solvent.

[0021] More preferably, in step (1), the reaction is carried out at 90° C. for 24 hours.

[0022] The beneficial effects of the present invention are:

[0023] 1. The present invention has good chemical selectivity when constructing 2-acyl-4-oxobutyrate derivatives.

[0024] 2. The raw materials used in the present invention are easily available, the yield is high, the reaction conditions are mild, the reaction time is short, the substrate range is wide, the reaction specificity is strong, and the post-processing is simple. DETAILED DESCRIPTION

[0025] The technical solution of the present invention is further illustrated and described below through specific implementation methods.

[0026] Example 1

[0027] Preparation of ethyl 2-benzoyl-4-oxo-4-phenylbutyrate

[0028]

[0029] 2-(dimethyl(oxo)-λ 6 1-(4-methoxyphenyl)ethane-1-one (0.1 mmol), diethyl malonate (0.1 mmol), and 1 mL of acetonitrile were added to a 15 mL reaction tube and placed in a 90°C oil bath under air for 24 hours. After cooling to room temperature, the reaction solution was diluted with ethyl acetate and washed three times with water. The organic phase was dried over anhydrous NaSO, filtered, concentrated, and purified by column chromatography to obtain 18.8 mg of the desired product in a 61% yield. The NMR characterization of the desired product is as follows: 1 H NMR(500MHz, CDCl3)δ7.99–7.95(m,2H),6.94(d,J=8.8Hz,2H),4.27–4.20(m,4H) ,4.05(t,J=7.1Hz,1H),3.88(s,3H),3.59(d,J=7.1Hz,2H),1.29(t,J=7.1Hz,6H). 13 C NMR (126MHz, CDCl3) δ195.1,169.3,163.9,130.5,129.3,113.9,61.8,55.6,47.4,37.5,14.1.

[0030] Example 2

[0031] Preparation of ethyl 2-acetyl-4-(4-methoxyphenyl)-4-oxobutanoate

[0032]

[0033] 2-(dimethyl(oxo)-λ 6 1-(4-methoxyphenyl)ethane-1-one (0.1 mmol), ethyl acetoacetate (0.1 mmol), and 1 mL of acetonitrile were added to a 15 mL reaction tube and placed in a 90°C oil bath under air for 24 hours. After cooling to room temperature, the reaction solution was diluted with ethyl acetate and washed three times with water. The organic phase was dried over anhydrous NaSO, filtered, concentrated, and purified by column chromatography to obtain 14.7 mg of the desired product in a 53% yield. The NMR characterization of the desired product is as follows: 1 H NMR (500MHz, CDCl3) δ7.96(d,J=8.9Hz,2H),6.94(d,J=8.9Hz,2H),4.22(q,J=7.1Hz,3H),3.87(s,3 H),3.68(dd,J=18.2,8.3Hz,1H),3.48(dd,J=18.2,5.6Hz,1H),2.45(s,3H),1.29(t,J=7.1Hz,3H). 13 C NMR (126MHz, CDCl3) δ202.7,195.6,169.1,163.8,130.5,129.2,113.8,61.8,55.6,54.0,37.2,30.4,14.1.

[0034] Example 3

[0035] Preparation of methyl 4-(4-methoxyphenyl)-2-(4-methylbenzoyl)-4-oxobutanoate

[0036]

[0037] 2-(dimethyl(oxo)-λ 6 1-(4-methoxyphenyl)ethane-1-one (0.1 mmol), methyl 3-oxo-3-(p-tolyl)propionate (0.1 mmol), and 1 mL of acetonitrile were added to a 15 mL reaction tube and placed in a 90°C oil bath under air for 24 hours. After cooling to room temperature, the reaction solution was diluted with ethyl acetate and washed three times with water. The organic phase was dried over anhydrous NaSO, filtered, concentrated, and purified by column chromatography to obtain 25.8 mg of the desired product in a 76% yield. The NMR characterization of the desired product is as follows: 1H NMR (500MHz, CDCl3) δ8.01–7.95(m,4H),7.30(d,J=7.9Hz,2H),6.93(d,J=8.9H z,2H),5.12(t,J=6.8Hz,1H),3.86(s,3H),3.71(d,J=11.0Hz,5H),2.42(s,3H). 13 C NMR (126MHz, CDCl3) δ195.4,194.5,170.1,163.9,144.7,133.5,130.6,129.6 ,129.2,129.2,113.9,55.6,52.8,48.5,38.1,21.8.HRMS(ESI-TOF)m / z:calcd forC20H21O5+:341.1384(M+H)+,found:341.1384.

[0038] Example 4

[0039] Preparation of methyl 4-(4-methoxyphenyl)-2-(3-methylbenzoyl)-4-oxobutanoate

[0040]

[0041] 2-(dimethyl(oxo)-λ 6 1-(4-methoxyphenyl)ethane-1-one (0.1 mmol), methyl 3-oxo-3-(m-tolyl)propionate (0.1 mmol), and 1 mL of acetonitrile were added to a 15 mL reaction tube and placed in a 90°C oil bath under air for 24 hours. After cooling to room temperature, the reaction solution was diluted with ethyl acetate and washed three times with water. The organic phase was dried over anhydrous NaSO, filtered, concentrated, and purified by column chromatography to obtain 24.1 mg of the desired product in a 71% yield. The NMR characterization of the desired product is as follows: 1 H NMR(500MHz, CDCl3)δ8.00–7.95(m,2H),7.90(dd,J=6.7,1.8Hz,2H),7.44–7.37(m,2H),6. 95–6.91(m,2H),5.13(dd,J=7.4,6.3Hz,1H),3.86(s,3H),3.78–3.67(m,5H),2.43(s,3H). 13C NMR (126MHz, CDCl3) δ195.4,195.2,170.1,163.9,138.7,136.2,134.6,130.6,129.5 ,129.3,128.7,126.3,113.9,55.6,52.9,48.7,38.1,21.5.HRMS(ESI-TOF)m / z:calcd for C 20 H 21 O5 + :341.1384(M+H) + ,found:341.1384.

[0042] Example 5

[0043] Preparation of methyl 2-(4-methoxybenzoyl)-4-(4-ethoxyphenyl)-4-oxobutanoate

[0044]

[0045] 2-(dimethyl(oxo)-λ 6 1-(4-methoxyphenyl)ethane-1-one (0.1 mmol), methyl 3-(4-methoxyphenyl)-3-oxopropanoate (0.1 mmol), and 1 mL of acetonitrile were added to a 15 mL reaction tube and placed in a 90°C oil bath under air for 24 hours. After cooling to room temperature, the reaction solution was diluted with ethyl acetate and washed three times with water. The organic phase was dried over anhydrous NaSO, filtered, concentrated, and purified by column chromatography to obtain 26.0 mg of the desired product in a 73% yield. The NMR characterization of the desired product is as follows: 1 H NMR (500MHz, CDCl3) δ8.14–8.07(m,2H),8.02–7.95(m,2H),7.03–6.90(m,4H),5.11(d,J=6.3Hz,1H),3.88(dd,J=7.4,5.0Hz,6H),3.76–3.67(m,5H). 13 C NMR (126MHz, CDCl3) δ195.5,193.3,170.2,164.1,163.9,131.5,130.6,129.3,129.0,114.1,113.9,55.6,55.6,52.8,48.4,38.1.

[0046] Example 6

[0047] Preparation of methyl 2-(3-methoxybenzoyl)-4-(4-methoxyphenyl)-4-oxobutanoate

[0048]

[0049] 2-(dimethyl(oxo)-λ 6 1-(4-methoxyphenyl)ethane-1-one (0.1 mmol), methyl 3-(3-methoxyphenyl)-3-oxopropanoate (0.1 mmol), and 1 mL of acetonitrile were added to a 15 mL reaction tube and placed in a 90°C oil bath under air for 24 hours. After cooling to room temperature, the reaction solution was diluted with ethyl acetate and washed three times with water. The organic phase was dried over anhydrous NaSO, filtered, concentrated, and purified by column chromatography to obtain 28.2 mg of the desired product in a 79% yield. The NMR characterization of the desired product is as follows: 1 H NMR (500MHz, CDCl3) δ8.01–7.94(m,2H),7.70(dt,J=7.7,1.3Hz,1H),7.59(dd,J=2.7,1.5Hz,1H),7.41(t,J=7.9Hz,1H),7.15(ddd,J=8.2 ,2.6,1.0Hz,1H),6.98–6.90(m,2H),5.11(dd,J=7.6,6.1Hz,1H),3.85(d,J=1.2Hz,6H),3.78(dd,J=18.0,7.7Hz,1H),3.73–3.65(m,4H). 13 C NMR (126MHz, CDCl3) δ195.3,194.8,170.0,163.9,160.0,137.4,130.6,129.8,129.2 ,121.7,120.4,113.9,113.0,55.6,55.5,52.8,48.8,38.1.HRMS(ESI-TOF)m / z:calcd for C 20 H 21 O6 + :357.1333(M+H) + ,found:357.1333.

[0050] Example 7

[0051] Preparation of methyl 2-(4-bromobenzoyl)-4-(4-methoxyphenyl)-4-oxobutanoate

[0052]

[0053] 2-(dimethyl(oxo)-λ 61-(4-methoxyphenyl)ethane-1-one (0.1 mmol), methyl 3-(4-bromophenyl)-3-oxopropanoate (0.1 mmol), and 1 mL of acetonitrile were added to a 15 mL reaction tube and placed in a 90°C oil bath under air for 24 hours. After cooling to room temperature, the reaction solution was diluted with ethyl acetate and washed three times with water. The organic phase was dried over anhydrous NaSO, filtered, concentrated, and purified by column chromatography to obtain 30.1 mg of the desired product in a 75% yield. The NMR characterization of the desired product is as follows: 1 H NMR(500MHz, CDCl3)δ7.97(t,J=2.4Hz,2H),7.96(t,J=2.5Hz,2H),7.67–7.62(m,2 H),6.95–6.91(m,2H),5.06(dd,J=8.3,5.4Hz,1H),3.88–3.80(m,4H),3.70(s,4H). 13 C NMR(126MHz, CDCl3)δ195.3,194.1,169.6,164.0,135.0,132.2,130.6,130.6,129.1,129.0,113.9,55.6,53.0,48.5,38.2.HRMS(ESI-TOF)m / z:calcd forC 19 H 18 BrO5 + :405.0332(M+H) + ,found:405.0332.

[0054] Example 8

[0055] Preparation of ethyl 2-benzoyl-4-oxo-4-phenylbutyrate

[0056]

[0057] 2-(dimethyl(oxo)-λ 6 1-(2-(2-(2-(2-sulfimide)-1-phenylethane-1-one) (0.1 mmol), ethyl 3-oxo-3-phenylpropionate (0.1 mmol), and 1 mL of acetonitrile were added to a 15 mL reaction tube and placed in a 90°C oil bath under air for 24 hours. After cooling to room temperature, the reaction solution was diluted with ethyl acetate and washed three times with water. The organic phase was dried over anhydrous NaSO, filtered, concentrated, and purified by column chromatography to obtain 22.5 mg of the desired product in a 73% yield. The NMR characterization of the desired product is as follows: 1H NMR (500MHz, CDCl3) δ8.10 (dt, J=8.2, 1.0Hz, 2H), 8.00 (dq, J=8.1, 1.5Hz, 2H), 7.63–7.55 (m, 2H), 7.53–7.44 (m, 4H), 5.13 (dd, J=7. 6,6.0Hz,1H),4.16(qd,J=7.1,1.1Hz,2H),3.82(dd,J=18.2,7.5Hz,1H),3.73(dd,J=18.1,6.1Hz,1H),1.17(td,J=7.0,1.0Hz,3H). 13 C NMR (126MHz, CDCl3) δ197.0,194.9,169.4,136.1,133.7,133.6,129.0,128.8,128.7,128.3,61.9,48.9,38.2,14.0.

[0058] Example 9

[0059] Preparation of ethyl 2-benzoyl-4-(4-bromophenyl)-4-oxobutanoate

[0060]

[0061] 1-(4-bromophenyl)-2-(dimethyl(oxo)-λ 6 1-[(-sulfimide)-ethane-1-one (0.1 mmol), ethyl 3-oxo-3-phenylpropionate (0.1 mmol), and 1 mL of acetonitrile were added to a 15 mL reaction tube and placed in a 90°C oil bath under air for 24 hours. After cooling to room temperature, the reaction solution was diluted with ethyl acetate and washed three times with water. The organic phase was dried over anhydrous NaSO, filtered, concentrated, and purified by column chromatography to obtain 27.6 mg of the desired product in a 71% yield. The NMR characterization of the desired product is as follows: 1 H NMR (500MHz, CDCl3) δ8.12–8.07(m,2H),7.89–7.84(m,2H),7.64–7.59(m,3H),7.51(dd,J=8.4,7.1Hz,2H),5.11(dd,J=7 .7,5.9Hz,1H),4.16(q,J=7.1Hz,2H),3.78(dd,J=18.2,7.7Hz,1H),3.67(dd,J=18.2,6.0Hz,1H),1.17(t,J=7.1Hz,3H). 13C NMR (126MHz, CDCl3) δ196.1,194.7,169.2,136.1,134.9,133.8,132.1,129.8,129.1,128.9,128.8,62.0,48.9,38.2,14.0.

[0062] Example 10

[0063] Preparation of ethyl 2-benzoyl-4-oxo-4-(2-thienyl)butanoate

[0064]

[0065] 2-(dimethyl(oxo)-λ 6 1-(2-thienyl)ethane-1-one (0.1 mmol), ethyl 3-oxo-3-phenylpropionate (0.1 mmol), and 1 mL of acetonitrile were added to a 15 mL reaction tube and placed in a 90°C oil bath under air for 24 hours. After cooling to room temperature, the reaction solution was diluted with ethyl acetate and washed three times with water. The organic phase was dried over anhydrous NaSO, filtered, concentrated, and purified by column chromatography to obtain 19.9 mg of the desired product in a 63% yield. The NMR characterization of the desired product is as follows: 1 H NMR (500MHz, CDCl3) δ8.11–8.06(m,2H),7.83(dd,J=3.8,1.2Hz,1H),7.66(dd,J=4.9,1.1Hz,1H),7.63–7.57(m,1H),7.50(d d,J=8.4,7.2Hz,2H),7.15(dd,J=5.0,3.8Hz,1H),5.12(dd,J=7.5,6.2Hz,1H),4.16(q,J=7.1Hz,2H),1.16(t,J=7.1Hz,3H). 13 CNMR(126MHz, CDCl3)δ194.8,189.9,169.2,143.2,136.1,134.2,133.8,132.7,129.1,128.8,128.4,62.0,48.9,38.6,14.0.

[0066] Example 11

[0067] Preparation of ethyl 2-benzoyl-4-oxo-4-(2-phenoxyphenyl)butyrate

[0068]

[0069] 2-(dimethyl(oxo)-λ 61-(2-phenoxyphenyl)ethane-1-one (0.1 mmol), ethyl 3-oxo-3-phenylpropionate (0.1 mmol), and 1 mL of acetonitrile were added to a 15 mL reaction tube and placed in a 90°C oil bath under air for 24 hours. After cooling to room temperature, the reaction solution was diluted with ethyl acetate and washed three times with water. The organic phase was dried over anhydrous NaSO, filtered, concentrated, and purified by column chromatography to obtain 28.6 mg of the desired product in a 71% yield. The NMR characterization of the desired product is as follows: 1 H NMR(500MHz, CDCl3)δ8.08–8.01(m,2H),7.86(dd,J=7.9,1.8Hz,1H),7.62–7.55(m,1H),7.4 8(dd,J=8.4,7.1Hz,2H),7.42(ddd,J=8.3,7.3,1.8Hz,1H),7.39–7.35(m,2H),7.19–7.12(m, 2H),7.07–7.02(m,2H),6.87(dd,J=8.4,1.0Hz,1H),5.08(dd,J=7.5,6.1Hz,1H),4.12(q,J=7 .1Hz,2H),3.86(dd,J=18.8,7.5Hz,1H),3.78(dd,J=18.8,6.1Hz,1H),1.12(t,J=7.1Hz,3H). 13 C NMR (126MHz, CDCl3) δ197.9,195.0,169.6,157.0,156.0,136.2,134.1,133.6,130.9,130.2,129 .0,129.0,128.8,124.3,123.4,119.6,118.8,61.7,49.5,43.0,14.0.HRMS(ESI-TOF)m / z:calcd for C 25 H 22 O5Na + :425.1359(M+Na) + ,found:425.1359.

[0070] Example 12

[0071] Preparation of ethyl (E)-2-benzoyl-4-oxo-6-phenylhexyl-5-enoate

[0072]

[0073] (E)-1-(dimethyl(oxo)-λ 64-(2-(2-(2-(2-((-((-sulfimide)-4-phenylbut-3-en-2-one (0.1 mmol), ethyl 3-oxo-3-phenylpropionate (0.1 mmol), and 1 mL of acetonitrile) were added to a 15 mL reaction tube and placed in a 90°C oil bath under air for 24 hours. After cooling to room temperature, the reaction solution was diluted with ethyl acetate and washed three times with water. The organic phase was dried over anhydrous NaSO, filtered, concentrated, and purified by column chromatography to obtain 15.5 mg of the desired product in a 46% yield. The NMR characterization of the desired product is as follows: 1 H NMR (500MHz, CDCl3) δ8.11–8.05(m,2H),7.63(d,J=16.3Hz,1H),7.60(d,J=7.4Hz,1H),7.57–7.53(m,2H),7.50(dd,J=8.4,7.2Hz,2H), 7.43–7.39(m,3H),6.77(d,J=16.2Hz,1H),5.06(dd,J=7.4,6.3Hz,1H),4.16(q,J=7.1Hz,2H),3.54–3.41(m,2H),1.17(t,J=7.1Hz,3H). 13 C NMR (126MHz, CDCl3) δ196.8,195.0,169.4,143.8,136.2,134.4,133.7,130.8,129 .1,129.1,128.8,128.5,125.6,61.9,48.9,39.8,14.1.HRMS(ESI-TOF)m / z:calcd for C21H21O4 + :337.1434(M+H) + ,found:337.1434.

[0074] Example 13

[0075] Preparation of 1-ethyl-4-propyl-2-benzoylsuccinate

[0076]

[0077] 2-(dimethyl(oxo)-λ 6 To a 15 mL reaction tube were added propyl acetate (0.1 mmol), ethyl 3-oxo-3-phenylpropionate (0.1 mmol), and 1 mL of acetonitrile. The mixture was placed in a 90°C oil bath under air and allowed to react for 24 hours. After cooling to room temperature, the reaction solution was diluted with ethyl acetate and washed three times with water. The organic phase was dried over anhydrous NaSO, filtered, concentrated, and purified by column chromatography to afford 14.0 mg of the desired product in a 48% yield. The desired product was characterized by NMR as follows: 1H NMR (500MHz, CDCl3) δ8.07–8.02(m,2H),7.63–7.58(m,1H),7.49(dd,J=8.5,7.1Hz,2H),4.87(dd,J=7.9,6.6Hz,1H),4.14(q,J=7.1Hz,2H),4.03(td ,J=6.7,1.2Hz,2H),3.11(dd,J=17.4,7.8Hz,1H),3.03(dd,J=17.4,6.6Hz ,1H),1.62(q,J=7.0Hz,2H),1.16(t,J=7.1Hz,3H),0.91(t,J=7.4Hz,3H). 13 C NMR(126MHz, CDCl3)δ194.3,171.5,168.8,136.0,133.8,129.0,128.8,66.8,61.9,49.7,33.4,22.0,14.0,10.4.HRMS(ESI-TOF)m / z:calcd forC 16 H 20 O5Na + :315.1203(M+Na) + ,found:315.1203.

[0078] The above description is merely a preferred embodiment of the present invention and therefore cannot be used to limit the scope of the present invention. In other words, equivalent changes and modifications made within the scope of the present invention and the contents of the specification should still fall within the scope of the present invention.

Claims

1. A method for preparing a 2-acyl-4-oxobutyrate derivative, characterized in that: The steps include: (1) After mixing β-carbonyl ester, sulfonium ylide, Lewis acid and organic solvent, react at 85-95°C for 20-25 hours under air atmosphere; the Lewis acid is lithium bromide; (2) diluting the material obtained in step (1) with ethyl acetate, washing with water, and separating the organic phase; (3) drying, filtering, concentrating and chromatographically purifying the organic phase obtained in step (2) to obtain the 2-acyl-4-oxobutyrate derivative; The above-mentioned β-carbonyl ester is diethyl malonate, ethyl acetoacetate, methyl 3-oxo-3-(p-tolyl)propionate, methyl 3-oxo-3-(m-tolyl)propionate, methyl 3-(4-methoxyphenyl)-3-oxopropionate, methyl 3-(3-methoxyphenyl)-3-oxopropionate or methyl 3-(4-bromophenyl)-3-oxopropionate; The above sulfonium ylide is 2-(dimethyl(oxo)-λ 6 -sulfonimide)-1-(4-methoxyphenyl)ethane-1-one, 2-(dimethyl(oxo)-λ 6 -sulfonimide)-1-phenylethane-1-one, 1-(4-bromophenyl)-2-(dimethyl(oxo)-λ 6 -sulfonimide)ethane-1-one, 2-(dimethyl(oxo)-λ 6 -sulfonimide)-1-(2-thienyl)ethane-1-one, 2-(dimethyl(oxo)-λ 6 -sulfonimide)-1-(2-phenoxyphenyl)ethan-1-one, (E) -1-(dimethyl(oxo)-λ 6 -sulfonimide)-4-phenylbut-3-en-2-one or 2-(dimethyl(oxo)-λ 6 -sulfonimide)propyl acetate; The above-mentioned 2-acyl-4-oxobutyrate derivatives are ethyl 2-benzoyl-4-oxo-4-phenylbutyrate, ethyl 2-acetyl-4-(4-methoxyphenyl)-4-oxobutyrate, methyl 4-(4-methoxyphenyl)-2-(4-methylbenzoyl)-4-oxobutyrate, methyl 4-(4-methoxyphenyl)-2-(3-methylbenzoyl)-4-oxobutyrate, methyl 2-(4-methoxybenzoyl)-4-(4-ethoxyphenyl)-4-oxobutyrate, methyl 2-(4-methoxybenzoyl)-4-(4-ethoxyphenyl)-4-oxobutyrate, and methyl 2-(3-methoxybenzoyl)-4-(4-methoxyphenyl)-4-oxobutyrate. methyl-4-oxobutanoate, methyl 2-(4-bromobenzoyl)-4-(4-methoxyphenyl)-4-oxobutanoate, ethyl 2-benzoyl-4-oxo-4-phenylbutyrate, ethyl 2-benzoyl-4-(4-bromophenyl)-4-oxobutyrate, ethyl 2-benzoyl-4-oxo-4-(2-thienyl)butyrate, ethyl 2-benzoyl-4-oxo-4-(2-phenoxyphenyl)butyrate, ethyl (E)-2-benzoyl-4-oxo-6-phenylhexyl-5-enoate or 1-ethyl-4-propyl-2-benzoylsuccinate.

2. The preparation method according to claim 1, wherein: The organic solvent is N,N -Dimethylformamide, N, N -Dimethylacetamide, 1,2-dichloroethane, toluene, 1,4-dioxane, tetrahydrofuran, hexafluoroisopropanol, isopropanol, or acetonitrile.

3. The preparation method according to claim 2, wherein: The organic solvent is acetonitrile.

4. The preparation method according to any one of claims 1 to 3, characterized in that: The molar ratio of the β-carbonyl ester, the sulfonium ylide and the Lewis acid is 1:1:

1.

5. The preparation method according to claim 4, wherein: In the step (1), the reaction is carried out at 90° C. for 24 hours.

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