CN110283067B - Synthetic method of 2, 4-dihydroxy-3, 3-dimethylbutyric acid - Google Patents
Synthetic method of 2, 4-dihydroxy-3, 3-dimethylbutyric acid Download PDFInfo
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- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
Abstract
The invention discloses a method for synthesizing 2, 4-dihydroxy-3, 3-dimethylbutyric acid, which comprises the following steps: (1) isobutyraldehyde and oxalyl chloride monoethyl ester are subjected to aldol condensation reaction under the action of RM to generate 3, 3-dimethyl-2, 4-dioxo ethyl butyrate; wherein M is an alkali metal, R is alkoxy, hydrogen, amino or alkyl; (2) the ethyl 3, 3-dimethyl-2, 4-dioxobutyrate is subjected to reduction reaction to generate ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate, and the ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate is subjected to hydrolysis reaction to obtain a target product. Compared with the existing synthesis method, the synthesis method provided by the invention does not use extremely toxic raw materials, has high operation safety, does not have harsh reaction conditions, is simple and convenient to operate, and is easy to control the reaction.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthetic method of 2, 4-dihydroxy-3, 3-dimethylbutyric acid.
Background
2, 4-dihydroxy-3, 3-dimethylbutyric acid is an important organic synthesis intermediate and a medicine intermediate, and can be used for synthesizing D-calcium pantothenate. Currently, there are three main methods for synthesizing 2, 4-dihydroxy-3, 3-dimethylbutyric acid:
the method comprises the following steps: tomasz Rowicki, Ludwik Synoradzki, etc. (Ind. Eng. chem. Res. 2006, 45, 1259-. The method uses the cyanide which is a highly toxic raw material, increases a great deal of difficulty for wastewater treatment and production operation, has more reaction steps, is easy to generate other side reactions, and has great difference in final yield due to different process conditions.
The second method comprises the following steps: in the U.S. Pat. No. 4124597, isobutyraldehyde and glyoxylic acid are used as raw materials, aldol condensation is carried out, disproportionation reaction is carried out under the action of strong base and formaldehyde, and 2, 4-dihydroxy-3, 3-dimethylbutyric acid is obtained by acidification. Although cyanide is avoided, the method has low yield and relatively high glyoxylic acid price, and industrial production has certain limitation.
The third method comprises the following steps: in the us patent 884966, isobutyraldehyde and formaldehyde are used as raw materials, and 2, 4-dihydroxy-3, 3-dimethylbutyric acid is obtained by aldol condensation and hydrolysis reaction. The method does not adopt cyanide, the raw materials are easy to obtain and low in price, but the reaction is carried out under strong alkali, the aldehyde is easy to disproportionate, the reaction is not easy to control, and the yield is low.
In view of this, the research and development of a synthetic method of 2, 4-dihydroxy-3, 3-dimethylbutyric acid, which has the advantages of easily available raw materials, no toxicity, simple and convenient operation and mild reaction conditions, is of great significance to the industrial production of 2, 4-dihydroxy-3, 3-dimethylbutyric acid.
Disclosure of Invention
The invention aims to overcome the technical defects and provides a synthesis method of 2, 4-dihydroxy-3, 3-dimethylbutyric acid, which has the advantages of easily available raw materials, no toxicity, simple and convenient operation and mild reaction conditions.
In order to achieve the technical purpose, the technical scheme of the invention provides a method for synthesizing 2, 4-dihydroxy-3, 3-dimethylbutyric acid, which comprises the following steps:
s1, isobutyraldehyde and oxalyl chloride monoethyl ester are subjected to aldol condensation reaction under the action of RM to generate 3, 3-dimethyl-2, 4-dioxo ethyl butyrate; wherein M is an alkali metal, and R is an alkoxy group;
s2, carrying out reduction reaction on the ethyl 3, 3-dimethyl-2, 4-dioxobutyrate to generate ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate, and carrying out hydrolysis reaction on the ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate to obtain a target product.
The synthetic method of the 2, 4-dihydroxy-3, 3-dimethylbutyric acid provided by the invention comprises the following synthetic route:
compared with the prior art, the invention has the beneficial effects that:
1. compared with the existing synthesis method of 2, 4-dihydroxy-3, 3-dimethylbutyric acid, the synthesis method provided by the invention has the advantages that an intermediate can be directly used for the next reaction without purification, the reaction conditions are not harsh, the operation is simple and convenient, and the reaction is easy to control;
2. the synthesis method of the 2, 4-dihydroxy-3, 3-dimethylbutyric acid provided by the invention does not use highly toxic raw materials, has higher operation safety and easily obtained raw materials, and reduces the production cost;
3. the synthesis method of 2, 4-dihydroxy-3, 3-dimethylbutyric acid provided by the invention has the advantages that the yield is high, the total reaction yield can reach 78.9%, and the synthesis method does not generate waste water containing highly toxic substances, meets the requirements of environment-friendly production and has good industrial value.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the embodiments described herein are merely illustrative of the present invention and are not intended to limit the present invention.
The invention provides a synthesis method of 2, 4-dihydroxy-3, 3-dimethylbutyric acid, which comprises the following steps:
(1) isobutyraldehyde and oxalyl chloride monoethyl ester are subjected to aldol condensation reaction under the action of RM to generate 3, 3-dimethyl-2, 4-dioxo ethyl butyrate; wherein M is an alkali metal, R is alkoxy, hydrogen, amino or alkyl;
(2) the ethyl 3, 3-dimethyl-2, 4-dioxobutyrate is subjected to reduction reaction to generate ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate, and the ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate is subjected to hydrolysis reaction to obtain the target product 2, 4-dihydroxy-3, 3-dimethylbutyrate.
In some preferred embodiments of the present invention, the aldol condensation reaction in step (1) is carried out at a temperature of-78 to 0 ℃ for 2 to 5 hours.
In some preferred embodiments of the present invention, the molar ratio of isobutyraldehyde, RM and oxalyl chloride monoethyl ester in step (1) is 2 to 5: 2-5: 1.
in some preferred embodiments of the invention, RM is sodium ethoxide or lithium diisopropylamide.
In some preferred embodiments of the present invention, the solvent for the aldol condensation reaction in step (1) is tetrahydrofuran or tert-butyl methyl ether, and the step of obtaining ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate further comprises: washing the reacted product with water, extracting and separating with ethyl acetate to obtain an ethyl acetate layer, and drying and concentrating the ethyl acetate layer to obtain oily 2, 4-dihydroxy-3, 3-dimethyl ethyl butyrate.
In some preferred embodiments of the present invention, the reduction reaction temperature in step (2) is 50 to 100 ℃, the reaction pressure is 10 to 20bar, and the reaction time is 2 to 4 hours.
In some preferred embodiments of the invention, ethyl 3, 3-dimethyl-2, 4-dioxobutyrate is reacted in step (2) in H2And the reaction product is subjected to reduction reaction with Pd-C, and the molar ratio of the ethyl 3, 3-dimethyl-2, 4-dioxobutyrate to the Pd-C is 1: 0.0005 to 0.001.
In some preferred embodiments of the present invention, the solvent for the reduction reaction in step (2) is ethanol, and further comprises the following steps after the reduction reaction to obtain ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate: and filtering the reaction product, recovering the catalyst Pd-C, and concentrating the filtrate to obtain oily 2, 4-dihydroxy-3, 3-dimethyl ethyl butyrate.
In some preferred embodiments of the present invention, the temperature of the hydrolysis reaction in step (2) is 80-100 ℃, and the reaction time is 0.5-2 h.
In some preferred embodiments of the present invention, the ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate in step (2) is subjected to a hydrolysis reaction in NaOH solution, and the molar ratio of ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate to NaOH is 1: 1 to 4.
In some preferred embodiments of the present invention, the hydrolysis reaction in step (2) further comprises: adjusting the pH value of the hydrolysis reaction product to 3-4 by using hydrochloric acid, extracting and separating by using ethyl acetate to obtain an ethyl acetate layer, and drying and concentrating the ethyl acetate layer to obtain a white solid 2, 4-dihydroxy-3, 3-dimethylbutyric acid.
The present invention will be described in further detail with reference to specific examples. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The experimental methods in the present invention are conventional methods unless otherwise specified.
The experimental materials used in the present invention were all purchased from the market unless otherwise specified.
Example 1:
embodiment 1 of the present invention provides a method for synthesizing 2, 4-dihydroxy-3, 3-dimethylbutyric acid, comprising the following steps:
(1) preparation of ethyl 3, 3-dimethyl-2, 4-dioxobutyrate: dissolving 10.0g (138.68 mmol) of isobutyraldehyde and 9.4g (138.68 mmol) of sodium ethoxide in 50ml of tetrahydrofuran, stirring and mixing uniformly, dropwise adding 9.5g (69.34 mmol) of oxalyl chloride monoethyl ester into the mixed solution at-5 ℃, reacting at-5 ℃ for 2h, washing the obtained reaction product with water, separating and extracting by ethyl acetate, washing an organic layer by saturated saline solution, recovering ethyl acetate under reduced pressure, drying and concentrating to obtain 9.6g of colorless oily 3, 3-dimethyl-2, 4-dioxo ethyl butyrate, and directly using the colorless oily 3, 3-dimethyl-2, 4-dioxo ethyl butyrate for the next reaction without purification;
(2) preparation of ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate: dissolving the ethyl 3, 3-dimethyl-2, 4-dioxobutyrate prepared in the step (1) in 20ml of ethanol, and reacting the ethyl 3, 3-dimethyl-2, 4-dioxobutyrate with Pd-C according to a molar ratio of 1: 0.0008, adding 10% of Pd/C, stirring and mixing, introducing hydrogen, stirring and reacting for 4 hours at the hydrogen pressure of 15bar and the temperature of 80 ℃, cooling a reaction product to normal temperature after the reaction is finished, filtering and recovering Pd-C, decompressing and recovering ethanol, concentrating to obtain 9.7g of colorless oily 2, 4-dihydroxy-3, 3-dimethyl ethyl butyrate, and directly using the colorless oily 2, 4-dihydroxy-3, 3-dimethyl ethyl butyrate for the next reaction without purification;
(3) preparation of 2, 4-dihydroxy-3, 3-dimethylbutyric acid: according to the molar ratio of the ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate to NaOH being 1: 2, adding 2mol/L NaOH solution into the ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate prepared in the step (2), stirring and mixing uniformly, and then carrying out hydrolysis reaction for 1h at 100 ℃ to obtain a hydrolysis reaction product; adjusting the pH value of a hydrolysis reaction product to 3-4 by using hydrochloric acid, extracting by using ethyl acetate, drying an obtained organic layer by using anhydrous calcium chloride, filtering, and concentrating a filtrate to obtain 8.1g of white solid 2, 4-dihydroxy-3, 3-dimethylbutyric acid, wherein the melting point of the white solid is 122-125 ℃ (a literature value: 124 ℃), and the total reaction yield is 78.9%.
Example 2:
embodiment 2 of the present invention provides a method for synthesizing 2, 4-dihydroxy-3, 3-dimethylbutyric acid, comprising the following steps:
(1) preparation of ethyl 3, 3-dimethyl-2, 4-dioxobutyrate: dissolving 10.0g (138.68 mmol) of isobutyraldehyde and 15g (138.68 mmol) of lithium diisopropylamide in 100ml of tert-butyl methyl ether, stirring and mixing uniformly, dropwise adding 9.5g (69.34 mmol) of oxalyl chloride monoethyl ester into the mixed solution at-20 ℃, reacting at-20 ℃ for 4h, washing the obtained reaction product with water, separating and extracting with ethyl acetate, washing the organic layer with saturated saline solution, recovering ethyl acetate under reduced pressure, drying and concentrating to obtain 9.0g of colorless oily 3, 3-dimethyl-2, 4-dioxoethyl butyrate, and directly using the colorless oily 3, 3-dimethyl-2, 4-dioxoethyl butyrate for next-step reaction without purification;
(2) preparation of ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate: dissolving the ethyl 3, 3-dimethyl-2, 4-dioxobutyrate prepared in the step (1) in 20ml of ethanol, and reacting the ethyl 3, 3-dimethyl-2, 4-dioxobutyrate with Pd-C according to a molar ratio of 1: 0.00085 of the reaction product is added with 10 percent Pd/C, after stirring and mixing, hydrogen is introduced, the reaction product is stirred and reacted for 4 hours under the hydrogen pressure of 15bar and the temperature of 80 ℃, the reaction product is cooled to normal temperature after the reaction is finished, Pd-C is recovered by filtration, ethanol is recovered by decompression, and then 8.8g of colorless oily 2, 4-dihydroxy-3, 3-dimethyl ethyl butyrate is obtained after concentration and is directly used for the next reaction without purification;
(3) preparation of 2, 4-dihydroxy-3, 3-dimethylbutyric acid: according to the molar ratio of the ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate to NaOH being 1: 2, adding 2mol/L NaOH solution into the ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate prepared in the step (2), stirring and mixing uniformly, and then carrying out hydrolysis reaction for 1h at 100 ℃ to obtain a hydrolysis reaction product; adjusting the pH value of a hydrolysis reaction product to 3-4 by using hydrochloric acid, extracting by using ethyl acetate, drying an obtained organic layer by using anhydrous calcium chloride, filtering, and concentrating a filtrate to obtain 7.6g of white solid 2, 4-dihydroxy-3, 3-dimethylbutyric acid, wherein the melting point of the white solid is 123-124 ℃ (a literature value: 124 ℃), and the total reaction yield is 74.0%.
Example 3:
embodiment 3 of the present invention provides a method for synthesizing 2, 4-dihydroxy-3, 3-dimethylbutyric acid, comprising the following steps:
(1) preparation of ethyl 3, 3-dimethyl-2, 4-dioxobutyrate: dissolving 15g (208.02 mmol) of isobutyraldehyde and 14.1g (207.20 mmol) of sodium ethoxide in 50ml of tetrahydrofuran, stirring and mixing uniformly, dropwise adding 9.5g (69.34 mmol) of oxalyl chloride monoethyl ester into the mixed solution at 0 ℃, reacting for 2 hours at 0 ℃, washing the obtained reaction product with water, separating and extracting by ethyl acetate, washing an organic layer by saturated saline solution, recovering the ethyl acetate under reduced pressure, drying and concentrating to obtain 10.2g of colorless oily 3, 3-dimethyl-2, 4-dioxoethyl butyrate, and directly using the colorless oily 3, 3-dimethyl-2, 4-dioxoethyl butyrate for the next reaction without purification;
(2) preparation of ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate: dissolving the ethyl 3, 3-dimethyl-2, 4-dioxobutyrate prepared in the step (1) in 20ml of ethanol, and reacting the ethyl 3, 3-dimethyl-2, 4-dioxobutyrate with Pd-C according to a molar ratio of 1: 0.0005 of the raw materials is added with 10 percent Pd/C, after stirring and mixing, hydrogen is introduced, the mixture is stirred and reacted for 2 hours under the hydrogen pressure of 10bar and the temperature of 100 ℃, the reaction product is cooled to normal temperature after the reaction is finished, Pd-C is recovered by filtration, ethanol is recovered by decompression, 9.8g of colorless oily 2, 4-dihydroxy-3, 3-dimethyl ethyl butyrate is obtained after concentration, and the colorless oily 2, 4-dihydroxy-3, 3-dimethyl ethyl butyrate is directly used for the next reaction without purification;
(3) preparation of 2, 4-dihydroxy-3, 3-dimethylbutyric acid: according to the molar ratio of the ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate to NaOH being 1: 1, adding 2mol/L NaOH solution into the ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate prepared in the step (2), stirring and mixing uniformly, and carrying out hydrolysis reaction for 2 hours at 80 ℃ to obtain a hydrolysis reaction product; adjusting the pH value of a hydrolysis reaction product to 3-4 by using hydrochloric acid, extracting by using ethyl acetate, drying an obtained organic layer by using anhydrous calcium chloride, filtering, and concentrating a filtrate to obtain 7.8g of white solid 2, 4-dihydroxy-3, 3-dimethylbutyric acid, wherein the melting point of the white solid is 122-124 ℃ (a literature value: 124 ℃), and the total reaction yield is 75.6%.
Example 4:
embodiment 4 of the present invention provides a method for synthesizing 2, 4-dihydroxy-3, 3-dimethylbutyric acid, comprising the following steps:
(1) preparation of ethyl 3, 3-dimethyl-2, 4-dioxobutyrate: dissolving 25g (346.7 mmol) of isobutyraldehyde and 23.6g (346.8 mmol) of sodium ethoxide in 50ml of tetrahydrofuran, stirring and mixing uniformly, dropwise adding 9.5g (69.34 mmol) of oxalyl chloride monoethyl ester into the mixed solution at-78 ℃, reacting for 5h at-78 ℃, washing the obtained reaction product with water, separating and extracting by ethyl acetate, washing the organic layer by saturated saline solution, recovering ethyl acetate under reduced pressure, drying and concentrating to obtain 10g of colorless oily 3, 3-dimethyl-2, 4-dioxobutyric acid ethyl ester, and directly using the colorless oily 3, 3-dimethyl-2, 4-dioxobutyric acid ethyl ester in the next step without purification;
(2) preparation of ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate: dissolving the ethyl 3, 3-dimethyl-2, 4-dioxobutyrate prepared in the step (1) in 20ml of ethanol, and reacting the ethyl 3, 3-dimethyl-2, 4-dioxobutyrate with Pd-C according to a molar ratio of 1: adding 10% Pd/C into 0.001, stirring and mixing, introducing hydrogen, stirring and reacting for 4 hours at the hydrogen pressure of 20bar and the temperature of 50 ℃, cooling the reaction product to normal temperature after the reaction is finished, filtering and recovering Pd-C, decompressing and recovering ethanol, concentrating to obtain 9.8g of colorless oily 2, 4-dihydroxy-3, 3-dimethyl ethyl butyrate, and directly using the colorless oily 2, 4-dihydroxy-3, 3-dimethyl ethyl butyrate for the next reaction without purification;
(3) preparation of 2, 4-dihydroxy-3, 3-dimethylbutyric acid: according to the molar ratio of the ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate to NaOH being 1: 4, adding 2mol/L NaOH solution into the ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate prepared in the step (2), stirring and mixing uniformly, and carrying out hydrolysis reaction for 2h at 80 ℃ to obtain a hydrolysis reaction product; adjusting the pH value of the hydrolysis reaction product to 3-4 by using hydrochloric acid, extracting by using ethyl acetate, drying the obtained organic layer by using anhydrous calcium chloride, filtering, and concentrating the filtrate to obtain 7.8g of white solid 2, 4-dihydroxy-3, 3-dimethylbutyric acid, wherein the melting point of the white solid is 123-.
The above-described embodiments of the present invention should not be construed as limiting the scope of the present invention. Any other corresponding changes and modifications made according to the technical idea of the present invention should be included in the protection scope of the claims of the present invention.
Claims (8)
1. A method for synthesizing 2, 4-dihydroxy-3, 3-dimethylbutyric acid, comprising the following steps:
s1, isobutyraldehyde and oxalyl chloride monoethyl ester are subjected to aldol condensation reaction under the action of RM to generate 3, 3-dimethyl-2, 4-dioxo ethyl butyrate; wherein M is an alkali metal, and R is an alkoxy group;
s2, carrying out reduction reaction on the ethyl 3, 3-dimethyl-2, 4-dioxobutyrate to generate ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate, and carrying out hydrolysis reaction on the ethyl 2, 4-dihydroxy-3, 3-dimethylbutyrate to obtain a target product;
in the step S1, the aldol condensation reaction temperature is-78-0 ℃, the reaction time is 2-5 hours, and the molar ratio of isobutyraldehyde to RM to oxalyl chloride monoethyl ester is 2-5: 2-5: 1, the solvent of the aldol condensation reaction is tetrahydrofuran or tert-butyl methyl ether.
2. The method of synthesizing 2, 4-dihydroxy-3, 3-dimethylbutyric acid according to claim 1, further comprising, prior to producing ethyl 2, 4-dihydroxy-3, 3-dimethylbutyric acid: washing the reacted product with water, extracting and separating with ethyl acetate to obtain ethyl acetate layer, drying and concentrating.
3. The method for synthesizing 2, 4-dihydroxy-3, 3-dimethylbutyric acid according to claim 1, wherein the reduction reaction temperature in step S2 is 50-100 ℃, the reaction pressure is 10-20 bar, and the reaction time is 2-4 h.
4. The method for synthesizing 2, 4-dihydroxy-3, 3-dimethylbutyric acid according to claim 1, wherein the ethyl 3, 3-dimethyl-2, 4-dioxobutyrate is reacted in H in step S22And the reaction product is subjected to reduction reaction with Pd-C, and the molar ratio of the ethyl 3, 3-dimethyl-2, 4-dioxobutyrate to the Pd-C is 1: 0.0005 to 0.001.
5. The method for synthesizing 2, 4-dihydroxy-3, 3-dimethylbutyric acid according to claim 1, wherein the solvent for the reduction reaction in step S2 is ethanol, and the method further comprises, after the reduction reaction, before the step of producing ethyl 2, 4-dihydroxy-3, 3-dimethylbutyric acid: and filtering the product after reaction, recovering the catalyst Pd-C, and concentrating the filtrate.
6. The method for synthesizing 2, 4-dihydroxy-3, 3-dimethylbutyric acid according to claim 1, wherein the hydrolysis reaction in step S2 is carried out at a temperature of 80-100 ℃ for a reaction time of 0.5-2 h.
7. The method for synthesizing 2, 4-dihydroxy-3, 3-dimethylbutyric acid according to claim 1, wherein the ethyl 2, 4-dihydroxy-3, 3-dimethylbutyric acid was subjected to hydrolysis in NaOH solution in step S2, and the molar ratio of ethyl 2, 4-dihydroxy-3, 3-dimethylbutyric acid to NaOH was 1: 1 to 4.
8. The method for synthesizing 2, 4-dihydroxy-3, 3-dimethylbutyric acid according to claim 1, wherein the step of, after the hydrolysis reaction in step S2, obtaining 2, 4-dihydroxy-3, 3-dimethylbutyric acid further comprises: adjusting the pH value of the hydrolysis reaction product to 3-4 by using hydrochloric acid, extracting and separating by using ethyl acetate to obtain an ethyl acetate layer, and drying and concentrating the ethyl acetate layer.
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