Preparation method of C5 halogen acid ester which is an important intermediate of apophorin and preparation method of apophorin

Abstract

The application provides a preparation method of an important intermediate C5 halo acid ester (4-halo-2-methyl-2-butenoic acid ethyl ester) of aspidin, which comprises using angelic acid as a raw material, and performing two-step reactions of oxidation and halogenation, so that the C5 halo acid ester can be prepared at a high yield. The application also relates to a preparation method of aspidin comprising the preparation steps of the aforementioned intermediate C5 halo acid ester. The method has the advantages of high product selectivity, short process route, high yield, low cost and the like, and the preparation process has a high degree of greenness, and has excellent industrial production potential.

Description

Technical Field

[0001] This invention relates to the field of chemical synthesis technology, specifically to a method for preparing C5 halogen ester (ethyl 4-halo-2-methyl-2-butenoate), a key intermediate of apoester, and a method for preparing apoester. Background Technology

[0002] β-Apo-8'-carotene ethyl ester, also known as apo-ester, is a type of carotenoid compound widely used for coloring food and feed. In the food industry, it is mainly used for coloring edible oils, margarine, jams, jellies, and beverages. In the feed industry, it is widely used for coloring poultry, especially the skin, shanks, and fat of broilers, as well as for coloring poultry egg yolks. It has a high precipitation rate in target tissues and is a highly efficient carotenoid additive.

[0003] 4-Halo-2-methyl-2-butenoate ethyl ester, also known as C5 halide ester, is a key intermediate in the synthesis of apoester, giving apoester synthesis advantages such as high trans content, simple process route, and low cost. It is currently widely used in industrial applications.

[0004] The main synthetic routes for ethyl 4-halo-2-methyl-2-butenoate that have been reported so far are as follows:

[0005] US Patent 4596889 describes the preparation of C5 bromate from methyl vinyl ketone via cyanation, hydrolysis esterification, bromination, and subsequent reaction with triethyl phosphite. The reaction route is as follows:

[0006]

[0007] This method has a complex route and a low overall yield. It also uses phosphorus tribromide as a brominating agent, which generates a large amount of phosphorus-containing wastewater, causing serious environmental pollution.

[0008] In 1987, Gary R. Beecher's research group reported a four-step reaction to prepare C5 bromate from butadiene. The reaction formulas are as follows:

[0009]

[0010] This method involves a long synthetic route and uses butadiene, which is unstable and highly irritating, as a raw material, making it difficult to apply industrially.

[0011] Therefore, it is still necessary to develop a green process route suitable for industrial production to efficiently prepare C5 bromate. Summary of the Invention

[0012] To address the problems existing in the prior art, the present invention aims to provide a method for preparing ethyl 4-halo-2-methyl-2-butenoate. This method has the advantages of high product selectivity, a short process route, high yield, and low cost. The route is green and environmentally friendly and suitable for industrial production.

[0013] Another object of the present invention is to provide a method for preparing apoester including the aforementioned intermediate preparation steps.

[0014] To achieve the above-mentioned objectives, the technical solution adopted by the present invention is as follows:

[0015] A method for preparing C5 halogen ester (ethyl 4-halo-2-methyl-2-butenoate), an important intermediate of apoester, includes a two-step reaction of angelic acid and oxidation to prepare C5 halogen ester.

[0016] In one specific implementation plan, the following steps are included:

[0017] 1) Add dilute acid solution to ethanol, then add angelic acid and reflux to esterify angelic acid. After complete esterification, remove ethanol, add solvent and compound oxidant to carry out oxidation reaction. After the oxidation reaction is completed, add quencher to obtain ethyl 4-hydroxy-2-methyl-2-butenoate.

[0018] 2) Using ethyl 4-hydroxy-2-methyl-2-butenoate as a raw material, C5 halide esters were prepared by halogenation reaction in the presence of a solvent and under the action of a halogenating agent.

[0019] In one specific implementation, the dilute acid solution in step 1) is selected from one or more of dilute sulfuric acid, dilute hydrochloric acid, and dilute nitric acid; preferably, the dilute acid solution is a dilute acid aqueous solution with a mass concentration of 5-20%; more preferably, the mass ratio of angelic acid to dilute acid solution is 1:0.2-0.5, and the dropping rate of the dilute acid solution is 0.1-0.6 g / min; the temperature of the reaction vessel is 20-60°C when the dilute acid solution is added; even more preferably, the reflux temperature is 80-130°C, and the reflux time is 2-8 h.

[0020] In one specific implementation, the mass ratio of angelic acid to ethanol in step 1) is 1:5 to 20; the solvent is selected from one or more of pyridine, tetrahydrofuran, and toluene; preferably, the mass ratio of angelic acid to solvent is 1:1 to 10.

[0021] In one specific implementation, the compound oxidant in step 1) includes a primary oxidant and a co-oxidant; preferably, the primary oxidant is selected from one or more of hydrogen peroxide, tert-butyl hydroperoxide, and sodium chlorate, and the co-oxidant is selected from one or more of ferric chloride and ferric bromide; more preferably, the mass ratio of angelic acid to the primary oxidant is 1:0.05 to 0.12, and the mass ratio of the primary oxidant to the co-oxidant is 1:0.01 to 0.10.

[0022] In one specific implementation, the oxidation reaction in step 1) is carried out at a temperature of -20 to 20°C for 1 to 5 hours.

[0023] In one specific implementation, the quenching agent in step 1) is an aqueous solution of sodium thiosulfate; more preferably, the mass concentration of the aqueous solution of sodium thiosulfate is 5-30%; and the mass ratio of angelic acid to sodium thiosulfate is 1:0.15-0.40.

[0024] In one specific implementation, the solvent in step 2) is selected from one or more of chloroform, dichloromethane, and ethyl acetate; preferably, the ratio of ethyl 4-hydroxy-2-methyl-2-butenoate to solvent is 1:1 to 5.

[0025] In one specific implementation, the halogenating agent in step 2) is selected from one or more of N-bromosuccinimide, phosphorus tribromide, and titanium tetrachloride; preferably, the mass ratio of ethyl 4-hydroxy-2-methyl-2-butenoate to the halogenating agent is 1:1.5 to 5; more preferably, the holding temperature of the halogenation reaction in step 2) is 20 to 80°C; and the holding time is 2 to 10 hours.

[0026] In one specific implementation, step 2) further includes the step of extracting and separating the reaction solution into saturated brine after the halogenation reaction is completed, and removing the solvent by vacuum distillation after separating the organic phase to obtain the C5 halogen ester; preferably, the mass ratio of ethyl 4-hydroxy-2-methyl-2-butenoate to saturated brine is 1:0.5-3.

[0027] On the other hand, a method for preparing apoester includes the aforementioned preparation step of the intermediate C5 halide ester.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] 1) This invention provides a new process route for preparing C5 halide esters. Using angelic acid as raw material, C5 halide esters can be prepared in high yield through two-step reactions of oxidation and halogenation.

[0030] 2) The method of the present invention has the advantages of high product selectivity, short process route, high yield and low cost. Therefore, the preparation process is highly green and has excellent potential for industrial production. Detailed Implementation

[0031] The following specific embodiments further illustrate the technical solution and effects of the present invention. These embodiments are for illustrative purposes only and are not intended to limit the scope of protection of the present invention. Simple modifications made to the present invention based on the concept of the present invention are all within the scope of protection claimed by the present invention.

[0032] A method for preparing the C5 halogen ester, a key intermediate of apoester, involves using angelic acid as a raw material and undergoing a one-step oxidative esterification reaction to obtain ethyl 4-hydroxy-2-methyl-2-butenoate intermediate, followed by a halogenation reaction to prepare the C5 halogen ester.

[0033] The reaction equation is as follows:

[0034]

[0035] The first step is the synthesis of ethyl 4-hydroxy-2-methyl-2-butenoate. This reaction uses angelic acid as a raw material, which undergoes esterification in a dilute acid solution. After removing the solvent, a compound oxidant is added to undergo an oxidation reaction to obtain ethyl 4-hydroxy-2-methyl-2-butenoate.

[0036] Specifically, the preparation method of ethyl 4-hydroxy-2-methyl-2-butenoate according to the present invention includes, for example, the following steps:

[0037] a) Add ethanol to the reaction vessel, then add dilute acid solution dropwise, controlling the temperature during the dropwise addition process. After the addition is complete, add angelic acid, then heat and reflux the reaction. After the reaction is complete, remove the solvents such as ethanol by vacuum distillation to obtain the intermediate mixture.

[0038] b) Cool the intermediate mixture to below room temperature, then add the solvent and compound oxidant, maintain the temperature for a certain period of time, and the reaction is complete.

[0039] c) After the reaction is complete, filter to remove part of the catalyst from the reaction solution, then add a certain concentration of sodium thiosulfate aqueous solution for washing to completely quench the oxidant and wash away other impurities. Remove the reaction solvent by distillation to obtain ethyl 4-hydroxy-2-methyl-2-butenoate with a purity >95%.

[0040] In step a), the carboxyl group of angelic acid undergoes an esterification reaction with ethanol to generate ethyl angelic acid. The ethanol pretreatment step avoids the influence of the carboxyl group on the oxidation reaction. The mass ratio of angelic acid to ethanol is 1:5 to 20, for example, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:12, 1:15, 1:18, 1:20, etc., preferably 1:8-10. The dilute acid solution is one or more of dilute sulfuric acid, dilute hydrochloric acid, and dilute nitric acid; the mass concentration of the dilute acid solution is a 5-20% aqueous solution, for example, 5%, 10%, 15%, or 20% dilute acid solutions, preferably 15% dilute sulfuric acid.

[0041] In this invention, the amount of dilute acid solution used is based on the mass of angelic acid, and the mass ratio of angelic acid to dilute acid solution is 1:0.2 to 0.5, for example, including but not limited to 1:0.2, 1:0.25, 1:0.3, 1:0.35, 1:0.4, 1:0.45, and 1:0.5, preferably 1:0.3 to 0.4. The dilute acid solution is preferably added slowly dropwise to the reaction solvent at a dropping rate of 0.1-0.6 g / min, for example, including but not limited to 0.1 g / min, 0.2 g / min, 0.3 g / min, 0.4 g / min, 0.5 g / min, and 0.6 g / min, preferably 0.2 g / min; the temperature of the reaction system during the dropwise addition of the dilute acid solution is 20-60℃, for example, 20℃, 25℃, 30℃, 35℃, 40℃, 45℃, 50℃, 55℃, and 60℃, preferably 35℃. In this invention, the reflux temperature is 80-130℃, such as 80℃, 85℃, 90℃, 95℃, 100℃, 105℃, 110℃, 115℃, 120℃, 125℃, 130℃, etc., preferably 90-100℃; the reflux time is 2-8h, such as 2h, 3h, 4h, 5h, 6h, 7h, 8h, etc., preferably 3-6h.

[0042] The solvent mentioned in step b) is selected from one or more of pyridine, tetrahydrofuran, and toluene, preferably tetrahydrofuran. The mass ratio of angelic acid to solvent is 1:1 to 10 based on the mass of angelic acid, for example 1:1, 1:2, 1:3, 1:5, 1:7, 1:9, 1:10, etc., preferably 1:2-5.

[0043] The compound oxidant includes a primary oxidant and a co-oxidant, wherein the primary oxidant is one or more of hydrogen peroxide, tert-butyl hydrogen peroxide, and sodium chlorate, preferably tert-butyl hydrogen peroxide; and the co-oxidant is one or more of ferric chloride and ferric bromide, preferably ferric bromide. Based on the mass of angelic acid, the mass ratio of angelic acid to the main oxidant is 1:0.05 to 0.12, for example, including but not limited to 1:0.05, 1:0.06, 1:0.07, 1:0.08, 1:0.09, 1:0.1, 1:0.11, 1:0.12, preferably 1:0.07 to 0.10; the mass ratio of the main oxidant to the co-oxidant is 1:0.01 to 0.10, for example, including but not limited to 1:0.01, 1:0.02, 1:0.03, 1:0.04, 1:0.05, 1:0.06, 1:0.07, 1:0.08, 1:0.09, 1:0.1, preferably 1:0.04 to 0.07.

[0044] In this invention, after adding the compound oxidant, the oxidation reaction temperature is maintained at -20 to 20°C, for example -20°C, -15°C, -10°C, -5°C, 0°C, 5°C, 10°C, 15°C, 20°C, etc., preferably -5 to 10°C; the oxidation reaction time is 1-5 hours, for example 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, etc., preferably 1.5-4 hours.

[0045] After the oxidation reaction in step c) is completed, some catalyst is removed from the reaction solution by filtration. Then, a certain concentration of sodium thiosulfate aqueous solution is added as a quencher and the mixture is washed to completely quench the oxidant and wash away other impurities. Specifically, the inorganic salts (ferric chloride, ferric bromide) in the compound oxidant are first removed by vacuum filtration, and then the quencher is added to quench the peroxide. The mass concentration of the sodium thiosulfate aqueous solution is 5-30%, including but not limited to 5%, 10%, 15%, 20%, 25%, and 30%, preferably 10-15%. Based on the mass of angelic acid, the mass ratio of angelic acid to sodium thiosulfate is 1:0.15-0.40, that is, the mass ratio of angelic acid to the actual mass of sodium thiosulfate contained in the added sodium thiosulfate aqueous solution, including but not limited to 1:0.15, 1:0.2, 1:0.25, 1:0.3, 1:0.35, and 1:0.4, preferably 1:0.18-0.25.

[0046] In this step, the distillation to remove the reaction solvent can be performed at an appropriate temperature depending on the type and boiling point of the solvent added, as is well known to those skilled in the art. After distillation to remove the solvent, ethyl 4-hydroxy-2-methyl-2-butenoate with a purity >95% is obtained, which serves as the starting material for the next halogenation reaction.

[0047] The second step involves using ethyl 4-hydroxy-2-methyl-2-butenoate as a raw material to undergo a halogenation reaction under the action of a halogenating agent to prepare C5 halide ester.

[0048] Specifically, the preparation method of the C5 halide ester includes the following steps:

[0049] a) Add solvent and ethyl 4-hydroxy-2-methyl-2-butenoate raw material to the reaction vessel, then add halogenated reagent. After adding halogenated reagent, keep warm for a certain time, take samples to analyze the conversion rate of ethyl 4-hydroxy-2-methyl-2-butenoate, and stop the reaction when the conversion rate is ≥99%.

[0050] b) Pour the reaction solution into saturated brine for extraction and phase separation. After separating the organic phase, remove the solvent by vacuum distillation to prepare the C5 halogen ester.

[0051] In the preparation of the C5 halogen ester, the solvent in step a) is one or more of chloroform, dichloromethane, and ethyl acetate, preferably chloroform; the mass ratio of ethyl 4-hydroxy-2-methyl-2-butenoate to the solvent is 1:1 to 5, for example 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, etc., preferably 1:2 to 3.5.

[0052] The added halogenating agent is one or more of N-bromosuccinimide, phosphorus tribromide, and titanium tetrachloride, preferably phosphorus tribromide; the ratio of ethyl 4-hydroxy-2-methyl-2-butenoate to the halogenating agent is 1:1.5 to 5, for example 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, etc., preferably 1:2 to 3.

[0053] After the halogenated reagent is added, the reaction is initiated at a temperature of 20-80℃, including but not limited to 20℃, 25℃, 30℃, 35℃, 40℃, 45℃, 50℃, 55℃, 60℃, 65℃, 70℃, 75℃, and 80℃, preferably 40-60℃; the holding time is 2-10 hours, including but not limited to 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, and 10 hours, preferably 4-6 hours. Specifically, samples can be taken to analyze the conversion rate of ethyl 4-hydroxy-2-methyl-2-butenoate. The reaction is considered complete when the conversion rate is ≥99%. Conventional analytical methods can be used, such as gas chromatography.

[0054] In step b), the reaction solution from step a) is poured into saturated brine for extraction and phase separation. After separating the organic phase, the solvent is removed, for example by vacuum distillation, to obtain a relatively pure C5 halide ester. The mass ratio of ethyl 4-hydroxy-2-methyl-2-butenoate to saturated brine is 1:0.5 to 3, including but not limited to 1:0.5, 1:1, 1:1.5, 1:2, 1:2.5, and 1:3, preferably 1:1 to 2.

[0055] The technical solution of the present invention will be further described below through specific embodiments, but it is not limited thereto.

[0056] The main sources of the raw materials used in the following examples are as follows:

[0057] Angelica sinensis acid, 99% purity, from Beijing Huawi Ruike.

[0058] All other ingredients are standard raw materials, purchased directly from the market.

[0059] 4-Hydroxy-2-methyl-2-butenoic acid ethyl ester and C5 halide ester were analyzed using the following method:

[0060] Gas chromatography analysis: A C15 column with a length of 1.5m and an inner diameter of 3mm was used. The column temperature was 250℃, the flame ionization detector temperature was 320℃, the carrier gas was nitrogen, the flow rate was 20ml / min, the air flow rate was 200ml / min, the hydrogen flow rate was 50ml / min, and the injection rate was 0.5 μL.

[0061] Example 1

[0062] 1) Preparation of ethyl 4-hydroxy-2-methyl-2-butenoate:

[0063] 100g of ethanol was weighed into a reaction vessel, and the vessel was stirred and heated to 40℃. Then, 4g of 10% dilute hydrochloric acid was weighed and added dropwise to the reaction solvent at a rate of 0.3g / min. After the addition was complete, 10g of angelic acid was weighed and added to the reaction solution, and the mixture was heated to 100℃ and refluxed for 4.5h. After the angelic acid had reacted completely, the ethanol was removed by vacuum distillation. The mixture was then cooled to 5℃, and 25g of tetrahydrofuran, 0.7g of hydrogen peroxide, and 0.04g of ferric bromide were added. The reaction was continued at this temperature for 4h until the reaction was complete. The insoluble matter in the reaction solution was removed by filtration at room temperature. 19g of 10% sodium thiosulfate aqueous solution was added, and the organic phase was separated. The solvent was removed by vacuum distillation to obtain ethyl 4-hydroxy-2-methyl-2-butenoate with a purity of 95.3%.

[0064] 2) Preparation of C5 bromate:

[0065] 10g of the prepared ethyl 4-hydroxy-2-methyl-2-butenoate, 20g of dichloromethane, and 15g of phosphorus tribromide were weighed into a reaction vessel and heated to 35℃ for 4 hours. The reaction was stopped when the conversion rate of the raw materials was ≥99%. The reaction solution was poured into 10g of saturated brine for extraction and phase separation. After separating the dichloromethane phase, the solvent was removed by vacuum distillation to prepare C5 bromate with a purity of 98.3% and an overall yield of 91.5%.

[0066] Example 2

[0067] Preparation of ethyl 4-hydroxy-2-methyl-2-butenoate:

[0068] 80g of ethanol was weighed into a reaction vessel, the vessel was stirred, and the temperature was raised to 30℃. Then, 3g of 15% dilute sulfuric acid was weighed and added dropwise to the reaction solvent at a dropping rate of 0.2g / min. After the addition was complete, 10g of angelic acid was weighed and added to the reaction solution, and the mixture was heated to 90℃ and refluxed for 5 hours. After the angelic acid had reacted completely, the ethanol was removed by vacuum distillation. The temperature was then lowered to 10℃, and 20g of toluene, 1g of tert-butyl hydroperoxide, and 0.05g of ferric chloride were added. The reaction was continued at this temperature for 2 hours until the reaction was complete. The insoluble matter in the reaction solution was removed by filtration at room temperature. 13g of 15% sodium thiosulfate aqueous solution was added, and the organic phase was separated. The solvent was removed by vacuum distillation to obtain ethyl 4-hydroxy-2-methyl-2-butenoate with a purity of 96.1%.

[0069] Preparation of C5 chlorate:

[0070] 10g of the prepared ethyl 4-hydroxy-2-methyl-2-butenoate, 30g of chloroform, and 18g of titanium tetrachloride were weighed into a reaction vessel and heated to 50℃ for 5 hours. The reaction was stopped when the conversion rate of the raw materials was ≥99%. The reaction solution was poured into 15g of saturated brine for extraction and phase separation. After separating the chloroform phase, the solvent was removed by vacuum distillation to prepare C5 chloroester with a purity of 99.1%, and the overall yield was 89.8%.

[0071] Example 3

[0072] Preparation of ethyl 4-hydroxy-2-methyl-2-butenoate:

[0073] Weigh 50g of ethanol into a reaction vessel, turn on the stirrer, and heat to 60℃. Then, weigh 5g of 6% dilute sulfuric acid and add it dropwise to the reaction solvent at a rate of 0.55g / min. After the addition is complete, weigh 10g of angelic acid and add it to the reaction solution. Heat to 80℃ and reflux for 7 hours. After the angelic acid has reacted completely, remove the ethanol by vacuum distillation. Then, cool to -10℃, add 80g of pyridine, 0.5g of sodium chlorate, and 0.05g of ferric bromide, and continue the reaction at this temperature for 4 hours. The reaction is then complete. Filter to remove insoluble matter from the reaction solution at room temperature, add 16g of 25% sodium thiosulfate aqueous solution, then separate the organic phase. Remove the solvent by vacuum distillation to obtain ethyl 4-hydroxy-2-methyl-2-butenoate with a purity of 96.9%.

[0074] Preparation of C5 chlorate:

[0075] 10 g of the prepared ethyl 4-hydroxy-2-methyl-2-butenoate, 50 g of ethyl acetate, and 42 g of N-bromosuccinimide were weighed into a reaction vessel and heated to 80 °C for 7 h. The reaction was stopped when the conversion rate of the raw materials was ≥99%. The reaction solution was poured into 20 g of saturated brine for extraction and phase separation. The ethyl acetate phase was separated and the solvent was removed by vacuum distillation to prepare C5 chlorate ester with a purity of 99.3%, with an overall yield of 87.1%.

Claims

1. A method for preparing a C5 halide ester, an important intermediate of apoester, characterized in that, This includes the steps of preparing C5 halide esters from angelic acid through a two-step reaction of oxidation and halogenation, including the following steps: 1) Add dilute acid solution to ethanol, then add angelic acid and reflux to esterify angelic acid. After complete esterification, remove ethanol, add solvent and compound oxidant to carry out oxidation reaction. After the oxidation reaction is completed, add quencher to obtain ethyl 4-hydroxy-2-methyl-2-butenoate. 2) Using ethyl 4-hydroxy-2-methyl-2-butenoate as a raw material, C5 halide esters were prepared by halogenation reaction in the presence of a solvent and under the action of a halogenating agent. The compound oxidant mentioned in step 1) includes a primary oxidant and a co-oxidant; The primary oxidant is selected from one or more of hydrogen peroxide, tert-butyl hydroperoxide, and sodium chlorate, and the auxiliary oxidant is selected from one or more of ferric chloride and ferric bromide.

2. The preparation method according to claim 1, characterized in that, In step 1), the dilute acid solution is selected from one or more of dilute sulfuric acid, dilute hydrochloric acid, and dilute nitric acid.

3. The preparation method according to claim 2, characterized in that, In step 1), the mass ratio of angelic acid to ethanol is 1:5-20.

4. The preparation method according to claim 2, characterized in that, The dilute acid solution is a dilute acid aqueous solution with a mass concentration of 5-20%.

5. The preparation method according to claim 4, characterized in that, The mass ratio of angelic acid to dilute acid solution is 1:0.2-0.5, the dropping rate of dilute acid solution is 0.1-0.6 g / min, and the temperature of the reaction vessel is 20-60℃ when the dilute acid solution is added.

6. The preparation method according to claim 5, characterized in that, The reflux temperature is 80–130°C, and the reflux time is 2–8 hours.

7. The preparation method according to claim 1, characterized in that, In step 1), the solvent is selected from one or more of pyridine, tetrahydrofuran, and toluene.

8. The preparation method according to claim 7, characterized in that, The mass ratio of angelic acid to solvent is 1:1 to 10.

9. The preparation method according to claim 1, characterized in that, The mass ratio of angelic acid to the main oxidant is 1:0.05 to 0.12, and the mass ratio of the main oxidant to the co-oxidant is 1:0.01 to 0.

10.

10. The preparation method according to claim 1, characterized in that, The oxidation reaction in step 1) is carried out at a temperature of -20 to 20°C for 1 to 5 hours.

11. The preparation method according to claim 1, characterized in that, In step 2), the solvent is selected from one or more of chloroform, dichloromethane, and ethyl acetate.

12. The preparation method according to claim 11, characterized in that, The ratio of ethyl 4-hydroxy-2-methyl-2-butenoate to solvent is 1:1 to 5.

13. The preparation method according to claim 11, characterized in that, The quenching agent is an aqueous solution of sodium thiosulfate.

14. The preparation method according to claim 13, characterized in that, The sodium thiosulfate aqueous solution has a mass concentration of 5-30%; the mass ratio of angelic acid to sodium thiosulfate is 1:0.15-0.

40.

15. The preparation method according to claim 1, characterized in that, In step 2), the halogenated reagent is selected from one or more of N-bromosuccinimide, phosphorus tribromide, and titanium tetrachloride.

16. The preparation method according to claim 15, characterized in that, The mass ratio of ethyl 4-hydroxy-2-methyl-2-butenoate to the halogenated reagent is 1:1.5 to 5.

17. The preparation method according to claim 16, characterized in that, In step 2), the halogenation reaction is kept at a temperature of 20–80°C for 2–10 hours.

18. The preparation method according to claim 15, characterized in that, Step 2) further includes the step of extracting and separating the reaction solution into saturated brine after the halogenation reaction is completed, and removing the solvent by vacuum distillation after separating the organic phase to obtain the C5 halogen ester.

19. The preparation method according to claim 18, characterized in that, The mass ratio of ethyl 4-hydroxy-2-methyl-2-butenoate to saturated brine is 1:0.5-3.

20. A method for preparing apocyanide, characterized in that, The preparation steps of the intermediate C5 halogen ester as described in any one of claims 1 to 19 are included.

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