Preparation method of a-deuterated carboxylic acid derivative compound

Abstract

The invention relates to the technical field of heterogeneous catalysis organic synthesis chemistry, and discloses a preparation method of an a-deuterated carboxylic acid derivative compound. The alpha-deuterated carboxylic acid derivative is obtained by taking carboxylic acid and a derivative thereof as reactants and taking X zeolite as a heterogeneous catalyst in the presence of a deuterated reagent through direct and efficient reaction. The method has the advantages of simple operation, mild reaction conditions, good substrate universality and the like, and shows good potential in the aspect of drug intermediate synthesis.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, relates to the synthesis of α-deuterated carboxylic acid derivatives, and discloses a method for hydrogen-deuterium exchange of α-carboxylic acid compounds catalyzed by a heterogeneous catalyst. Background Art

[0002] Since the discovery of deuterium atoms, the deuterium substitution process has played a huge role in organic synthesis, mechanism research and spectral / microscopic analysis. Since the 1960s, the deuterium substitution process has been widely used in drug metabolism and pharmacokinetics, including absorption, distribution and metabolism research. Due to the difference in bond length and bond energy between CH and CD bonds, when deuterium is located at the step that affects the reaction rate, it can reduce the drug metabolism rate and prolong the drug's residence time in the human body.

[0003] Cyclic carboxylic acids are widely used in medicinal chemistry, such as nonsteroidal anti-inflammatory drugs and various natural products. In addition to themselves, carboxylic acid compounds and their derivatives are very important for the construction of drug molecules and polymer materials; for example, carboxylic acid compounds can be converted into esters and amides by condensation, alcohols by hydride reduction, and amines by Curtius rearrangement. In addition, the carboxylic acid part can act as an alkyl radical to further construct a multifunctional carbon framework through transition metal and photoredox. Therefore, the development of highly selective and green methods for the deuterated carboxylic acid derivatives is of great significance for the research and development of deuterated drugs and deuterated materials.

[0004] The synthesis methods of α-deuterated carboxylic acid derivatives are mainly divided into multi-step synthesis method and direct hydrogen-deuterium exchange: the multi-step synthesis method first deuterates the aldehyde with stronger aH, and then the a-deuterated aldehyde is oxidized to α-deuterated carboxylic acid; compared with the multi-step synthesis method, the direct hydrogen-deuterium exchange simplifies the reaction path and is more suitable for industrial production. However, most direct hydrogen-deuterium exchange methods use noble metal catalysts while adding strong bases, or use directing groups to increase the acidic site of the a-position H, and have low selectivity, which is not conducive to green environmental protection.

[0005] X zeolite has been widely used as a catalyst in industrial production, and is often used to adsorb CO2 and volatile organic compounds (VOCs). Compared with traditional strong bases, the FAU topological structure has a larger surface area and pore volume, which makes it have a stronger adsorption and desorption ability in chemical reactions, and its inherent alkalinity can reduce the possibility of acid-base neutralization side reactions. As a heterogeneous catalyst, X zeolite has stable properties and can be repeatedly used in catalytic reactions. It is a cost-effective alternative to strong bases. Summary of the invention

[0006] In order to simplify the production steps, reduce the production cost, and solve the problems of using strong base in the preparation process of α-deuterated carboxylic acid derivatives in the prior art, the present invention establishes an environmentally friendly H / D exchange method for carboxylic acid derivatives using X zeolite catalyst, which has the advantages of high deuteration rate, good regioselectivity and wide substrate application range.

[0007] The steps of synthesizing α-deuterated carboxylic acid and its derivatives involved in the present invention are as follows: adding the carboxylic acid derivatives and X zeolite catalyst involved into a reaction tube under air conditions, adding a deuterated reagent into the reaction system, placing the system into a heater under magnetic stirring conditions, quenching the reaction after the reaction is completed, centrifuging and filtering, collecting the supernatant liquid, and then analyzing and purifying the crude product by column chromatography to finally obtain the deuterated carboxylic acid and its derivatives.

[0008]

[0009] In the general formula (1), R 1 is selected from aryl or substituted aryl, heteroaryl or substituted heteroaryl; R 1 The substituent is alkyl, alkoxy, halogen, or trifluoromethyl; the aryl is phenyl, benzyl, biphenyl, naphthyl, or phenanthryl. The heteroaryl is selected from at least one of pyrrolyl, benzofuranyl, thienyl, and imidazolyl. R 2 is a H atom or an alkyl group; R 2 When it is an alkyl group, the hydrogen on the α-C will also be deuterated.

[0010] The deuterium donor reagent is selected from one or a combination of heavy water (D2O), deuterated methanol (MeOD), deuterated ethanol (EtOD), deuterated n-propanol (n-PrOD), deuterated isopropanol (i-PrOD), deuterated n-butanol (n-BuOD), deuterated tert-butanol (t-BuOD), and deuterated acetone;

[0011] The ratio of the molar amount of the carboxylic acid derivative compound to the mass of the X zeolite is 0.5:20 (mmol / mg); the reaction temperature is 80-150°C; the reaction time is 8-24h, and the mass ratio of the deuterated reagent to the X zeolite is greater than 25:1.

[0012] The reaction was quenched by chilling the reactor in ice water.

[0013] The catalyst in the present invention is an X zeolite catalyst, and the X zeolite catalyst is synthesized by referring to existing methods, such as:

[0014] Add appropriate amount of potassium hydroxide and distilled water to water glass, stir until the system cools to room temperature to form a mixed solution, then add sodium aluminate, stir for a period of time, put the mixture into an autoclave, crystallize at high temperature, filter, wash, dry and calcine at high temperature to obtain X zeolite, wherein the molar composition of each substance in the gel system is: Na2O: K2O: SiO2: Al2O3: H2O = 5-30: 5-7: 3-5: 2-3: 120-150.

[0015] Furthermore, the high temperature crystallization conditions are 60-100° C. for crystallization for 12-36 hours, and the high temperature calcination temperature is 550° C. to obtain the X zeolite, and the silicon-aluminum ratio in the zeolite synthesis system is 1.5-10.

[0016] The X zeolite obtained in the present invention has a specific surface area of ​​400 to 500 m 2 / g, the mesopore volume is 0.10~0.15m 3 / g, and the relative crystallinity is between 80 and 91%.

[0017] Compared with the prior art, the present invention has the following technical advantages:

[0018] (1) The present invention uses X zeolite catalyst to directly convert carboxylic acid derivative compounds into α-deuterated carboxylic acid derivative compounds;

[0019] (2) The H / D exchange reaction used in the method of the present invention has high regioselectivity, a wide range of substrate applicability, and no generation of multiple by-products. The product can be generated in an air atmosphere without the need for additional solvents, has high atom economy, is green and environmentally friendly, and is conducive to actual production. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 is the H NMR spectrum of deuterated p-bromophenylacetic acid in Example 1;

[0021] Figure 2 is the H NMR spectrum of deuterated p-methoxyphenylacetic acid in Example 2;

[0022] Figure 3 is the H NMR spectrum of deuterated p-trifluoromethylphenylacetic acid in Example 3;

[0023] Figure 4 is the H NMR spectrum of deuterated 2,6-dichlorophenylacetic acid in Example 4;

[0024] Figure 5 is the H NMR spectrum of deuterated naphthylacetic acid in Example 5;

[0025] Figure 6 The H NMR spectrum of deuterated 2,3-dihydrobenzofuranacetic acid in Example 6;

[0026] Figure 7 The H NMR spectrum of deuterated ethyl phenylacetate in Example 7. DETAILED DESCRIPTION

[0027] In order to more clearly understand the technical features, purposes and beneficial effects of the present invention, the technical solution of the present invention is described in detail below, but it should not be understood as limiting the scope of implementation of the present invention. The catalyst sources involved in the embodiments are:

[0028] The preparation method of X zeolite is as follows: 6.6g potassium hydroxide solid and 42.5g distilled water are added to 12.1ml water glass in sequence, and stirred until the system cools to room temperature to form a mixed solution. 5.9g sodium aluminate is added to the mixed solution, and the mixture is stirred evenly and then stirred continuously for 2 hours at room temperature. The mixture is then placed in an autoclave and placed in an oven at 60-100°C for static crystallization for 12-36 hours. After filtering, washing and drying, the mixture is placed in a muffle furnace at 550°C for calcination for 4 hours to obtain nano-X zeolite aggregates containing intercrystalline mesopores. The molar ratio of each component of the mixture in the reaction is Na2O: K2O: SiO2: Al2O3: H2O = 15:7:5:2:140.

[0029] The preparation method of TS-1 zeolite is as follows: 10.42g of tetraethyl orthosilicate is dripped into a mixed solution of 6.1g of TPAOH aqueous solution (mass fraction 25%) and 16.2g of deionized water, and then 6mL of isopropanol solution containing 0.425g of tetrabutyl titanate is slowly dripped under vigorous stirring. After stirring at 25°C for 4h, the mixed solution is transferred into a 100mL high-pressure reactor and crystallized at 180°C for 1d. The obtained product is filtered, washed, and dried in a vacuum oven at 100°C for 12h. The obtained solid powder is calcined at 550°C in an air atmosphere for 7h to obtain TS-1 molecular sieve. The molar ratio of each component of the mixture in the reaction is Na2O:TiO2:SiO2:H2O=0.3:8:2:135.

[0030] The preparation method of ZSM-5 zeolite is as follows: 100g silica sol is dispersed in 100g deionized water, then 18g n-butylamine solution is added, and the mixture is stirred for 1 hour at room temperature to prepare solution A; 2g Al2O3 powder (pseudo-boehmite) is dispersed in 100g deionized water, and the mixture is stirred for 1 hour at room temperature to prepare solution B. Then, solution B is slowly added dropwise to solution A under stirring to prepare a uniform gel, 2g NaOH solid is added to adjust the pH value of the gel, and the mixture is stirred for 1 hour, and then the mixture is loaded into a kettle, and crystallized at 170°C for about 24 hours, and then the ZSM-5 zeolite is obtained after cooling to room temperature, washing, drying, and calcining. The molar ratio of each substance is: NaOH: SiO2: Al2O3: H2O = 0.1:1:0.04:30. Specific embodiment 1:

[0032] In a 10ml Schlenk tube, 0.5mmol of p-bromophenylacetic acid, 20mg of X zeolite, and 0.5ml of deuterated water were added in sequence. After the operation was completed, the mixture was added to the heater, the reaction temperature was controlled at 130°C, and the reaction was stirred for 8h. After the reaction was completed, the mixture was cooled to room temperature, and the reaction system was centrifuged and filtered. The supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. The characterization data of the product are as follows: 1 H NMR (400MHz, Chloroform-d) δ: 7.45 (d, J = 8.5 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H).

[0033] The reaction structure is:

[0034] Specific embodiment 2:

[0036] In a 10ml Schlenk tube, 0.5mmol p-methoxyphenylacetic acid, 20mg X zeolite, and 0.5ml deuterated water were added in sequence. After the operation was completed, the mixture was added to the heater, the reaction temperature was controlled at 130°C, and the reaction was stirred for 8h. After the reaction was completed, the mixture was cooled to room temperature, and the reaction system was centrifuged and filtered. The supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. The characterization data of the product are as follows: 1 H NMR(400MHz,Chloroform-d)δ:7.28-7.19(m,1H),6.87-6.80(m,3H),3.78(s,3H).

[0037] The reaction structure is:

[0038] Specific embodiment 3:

[0040] In a 10ml Schlenk tube, 0.5mmol of p-trifluoromethylphenylacetic acid, 20mg of X zeolite, and 0.5ml of deuterated water were added in sequence. After the operation was completed, the mixture was added to the heater, the reaction temperature was controlled at 130°C, and the reaction was stirred for 8h. After the reaction was completed, the mixture was cooled to room temperature, and the reaction system was centrifuged and filtered. The supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. The characterization data of the product are as follows: 1 HNMR (400MHz, Chloroform-d) δ7.59-7.52 (m, 2H), 7.51-7.40 (m, 2H). The reaction structure is:

[0041] Specific embodiment 4:

[0043] In a 10ml Schlenk tube, add 0.5mmol of 2,6-dichlorophenylacetic acid, 20mg of X zeolite, and 0.5ml of deuterated water in sequence. After the operation is completed, add it to the heater, control the reaction temperature at 130℃, and stir the reaction for 8h. After the reaction is completed, cool to room temperature, centrifuge and filter the reaction system. Collect the supernatant and concentrate it under reduced pressure. The crude product is separated and purified by column chromatography to obtain the product. The characterization data of the product are as follows: 1 H NMR (400MHz, DMSO-d6) δ: 7.50-7.45 (m, 2H), 7.33 (dd, J = 8.6, 7.5Hz, 1H), 3.88 (d, J = 6.5Hz, 1H).

[0044] The reaction structure is:

[0045] Specific embodiment 5:

[0047] In a 10ml Schlenk tube, 0.5mmol naphthaleneacetic acid, 20mg X zeolite, and 0.5ml deuterated water were added in sequence. After the operation was completed, the mixture was added to the heater, the reaction temperature was controlled at 130°C, and the reaction was stirred for 8h. After the reaction was completed, the mixture was cooled to room temperature, and the reaction system was centrifuged and filtered. The supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. The characterization data of the product are as follows: 1 H NMR (400MHz, Chloroform-d) δ7.18-8.0 (m, 7H);

[0048] The reaction structure is:

[0049] Specific embodiment 6:

[0051] In a 10ml Schlenk tube, add 0.5mmol 2,3-dihydrobenzofuranacetic acid, 20mg X zeolite, and 0.5ml deuterated water in sequence. After the operation is completed, add it to the heater, control the reaction temperature at 130℃, and stir the reaction for 8h. After the reaction is completed, cool to room temperature, centrifuge and filter the reaction system. Collect the supernatant and concentrate it under reduced pressure. The crude product is separated and purified by column chromatography to obtain the product. The characterization data of the product are as follows: 1 H NMR (400MHz, CDCl3) δ3.19(t,J=8.5Hz,2H),3.56(s,2H),4.56(t,J=8.7Hz,2H),6.47(d,J=8.3Hz,1H),6.99(d,J=7.9Hz,1H),7.11(s,1H);

[0052] The reaction structure is:

[0053] Specific embodiment 7:

[0055] In a 10ml Schlenk tube, add 0.5mmol ethyl phenylacetate, 20mg X zeolite, and 0.5ml deuterated water in sequence. After the operation is completed, add it to the heater, control the reaction temperature at 130℃, and stir the reaction for 8h. After the reaction is completed, cool to room temperature, centrifuge and filter the reaction system. Collect the supernatant and concentrate it under reduced pressure. The crude product is separated and purified by column chromatography to obtain the product. The characterization data of the product are as follows: 1 H NMR (400MHz, CDCl3): δ = 7.29 (m, 5H), 4.14 (q, J = 7.2Hz, 2H), 3.59 (s, 0.04H), 1.25 (t, J = 7.6Hz, 3H) ppm.

[0056] The reaction result expression is:

[0057]

[0058] Table 1: Deuteration rate and yield test data of Examples 1-7

[0059]

[0060] Specific embodiment 8

[0062] In a 10 ml Schlenk tube, 0.5 mmol of p-bromophenylacetic acid, 20 mg of X zeolite, and 0.5 ml of deuterated water were added in sequence. After the operation was completed, the mixture was added to the heater, the reaction temperature was controlled at 70°C, and the reaction was stirred for 8 hours. After the reaction was completed, the mixture was cooled to room temperature, and the reaction system was centrifuged and filtered. The supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. Specific embodiment 9

[0064] In a 10 ml Schlenk tube, 0.5 mmol of p-bromophenylacetic acid, 20 mg of X zeolite, and 0.5 ml of deuterated water were added in sequence. After the operation was completed, the mixture was added to the heater, the reaction temperature was controlled at 90°C, and the reaction was stirred for 8 hours. After the reaction was completed, the mixture was cooled to room temperature, and the reaction system was centrifuged and filtered. The supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. Specific embodiment 10

[0066] In a 10 ml Schlenk tube, 0.5 mmol of p-bromophenylacetic acid, 20 mg of X zeolite, and 0.5 ml of deuterated water were added in sequence. After the operation was completed, the mixture was added to the heater, the reaction temperature was controlled at 110°C, and the reaction was stirred for 8 hours. After the reaction was completed, the mixture was cooled to room temperature, and the reaction system was centrifuged and filtered. The supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product. Specific embodiment 11

[0068] In a 10 ml Schlenk tube, 0.5 mmol of p-bromophenylacetic acid, 20 mg of X zeolite, and 0.5 ml of deuterated water were added in sequence. After the operation was completed, the mixture was added to the heater, the reaction temperature was controlled at 150°C, and the reaction was stirred for 8 hours. After the reaction was completed, the mixture was cooled to room temperature, and the reaction system was centrifuged and filtered. The supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product.

[0069] Table 2: Examples 8-11

[0070]

[0071] Example 12

[0072] 0.5 mmol of p-bromophenylacetic acid, 20 mg of X zeolite, and 0.5 ml of deuterated acetone were added to a 10 ml Schlenk tube in sequence. After the operation was completed, the mixture was added to a heater, the reaction temperature was controlled at 130°C, and the reaction was stirred for 8 hours. After the reaction was completed, the mixture was cooled to room temperature, and the reaction system was centrifuged and filtered. The supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product.

[0073] Embodiment 13

[0074] 0.5 mmol of p-bromophenylacetic acid, 20 mg of X zeolite, and 0.5 ml of deuterated dimethyl sulfoxide were added to a 10 ml Schlenk tube in sequence. After the operation was completed, the mixture was added to a heater, the reaction temperature was controlled at 130°C, and the reaction was stirred for 8 hours. After the reaction was completed, the mixture was cooled to room temperature, and the reaction system was centrifuged and filtered. The supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product.

[0075] Embodiment 14

[0076] In a 10 ml Schlenk tube, 0.5 mmol of p-bromophenylacetic acid, 20 mg of X zeolite, and 0.5 ml of deuterated methanol were added in sequence. After the operation was completed, the mixture was added to the heater, the reaction temperature was controlled at 130°C, and the reaction was stirred for 8 hours. After the reaction was completed, the mixture was cooled to room temperature, and the reaction system was centrifuged and filtered. The supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product.

[0077] Embodiment 15

[0078] 0.5 mmol of p-bromophenylacetic acid, 20 mg of X zeolite, and 0.5 ml of deuterated ethanol were added to a 10 ml Schlenk tube in sequence. After the operation was completed, the mixture was added to a heater, the reaction temperature was controlled at 130°C, and the reaction was stirred for 8 hours. After the reaction was completed, the mixture was cooled to room temperature, and the reaction system was centrifuged and filtered. The supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product.

[0079] Example 16

[0080] 0.5 mmol of p-bromophenylacetic acid, 20 mg of X zeolite, and 0.5 ml of deuterated isopropanol were added to a 10 ml Schlenk tube in sequence. After the operation was completed, the mixture was added to a heater, the reaction temperature was controlled at 130°C, and the reaction was stirred for 8 hours. After the reaction was completed, the mixture was cooled to room temperature, and the reaction system was centrifuged and filtered. The supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product.

[0081] Table 3: Examples 12-16

[0082]

[0083]

[0084] Comparative Example 1

[0085] In a 10ml Schlenk tube, 0.5mmol p-bromophenylacetic acid, 0.1mmol NaOH, 10mg X zeolite, and 0.5ml deuterated water were added in sequence. After the operation was completed, the mixture was added to the heater, the reaction temperature was controlled at 130°C, and the reaction was stirred for 8h. After the reaction was completed, the mixture was cooled to room temperature, and the reaction system was centrifuged and filtered. The supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product.

[0086] Comparative Example 2

[0087] In a 10 ml Schlenk tube, 0.5 mmol of p-bromophenylacetic acid, 20 mg of Beta zeolite (HBeta-M can be obtained by the method in (ACS Catal., 2018, 8, 9043-9055)), and 0.5 ml of deuterated water were added in sequence. After the operation was completed, the mixture was added to the heater, the reaction temperature was controlled at 130 °C, and the reaction was stirred for 8 hours. After the reaction was completed, the mixture was cooled to room temperature, and the reaction system was centrifuged and filtered. The supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product.

[0088] Comparative Example 3

[0089] In a 10ml Schlenk tube, 0.5mmol of p-bromophenylacetic acid, 20mg of TS-1 zeolite, and 0.5ml of deuterated water were added in sequence. After the operation was completed, the mixture was added to the heater, the reaction temperature was controlled at 130°C, and the reaction was stirred for 8h. After the reaction was completed, the mixture was cooled to room temperature, and the reaction system was centrifuged and filtered. The supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product.

[0090] Comparative Example 4

[0091] In a 10 ml Schlenk tube, 0.5 mmol of p-bromophenylacetic acid, 20 mg of ZSM-5 zeolite, and 0.5 ml of deuterated water were added in sequence. After the operation was completed, the mixture was added to the heater, the reaction temperature was controlled at 130 ° C, and the reaction was stirred for 8 hours. After the reaction was completed, the mixture was cooled to room temperature, and the reaction system was centrifuged and filtered. The supernatant was collected and concentrated under reduced pressure, and the crude product was separated and purified by column chromatography to obtain the product.

[0092] Table 4: Comparative Examples 1-4

[0093]

[0094]

[0095] The above describes the optional embodiments of the present invention to teach those skilled in the art how to implement and reproduce the present invention. The raw materials and equipment used in the present invention, unless otherwise specified, are all commonly used raw materials and equipment in the art; the methods used in the present invention, unless otherwise specified, are all conventional methods in the art. In order to teach the scheme of the present invention, some conventional technical aspects have been simplified and omitted.

Claims

1. A method for preparing an α-deuterated carboxylic acid derivative compound, characterized in that: The carboxylic acid derivative compound represented by formula (1) is reacted with X zeolite and a deuterium donor reagent to generate an α-deuterated carboxylic acid derivative compound represented by formula (2); In the general formula (1), R 1 is selected from aryl, substituted aryl, heterocyclic group, substituted heterocyclic group; R 2 is H or alkyl.

2. The method for preparing the α-deuterated carboxylic acid derivative compound according to claim 1, characterized in that: The substituents on the substituted aryl and substituted heterocyclic groups are alkyl, alkoxy, halogen, and trifluoromethyl; the aryl group is phenyl, benzyl, biphenyl, naphthyl, and phenanthryl; and the heteroaryl group is selected from one of pyrrolyl, benzofuranyl, thienyl, and imidazolyl.

3. The method for preparing the α-deuterated carboxylic acid derivative compound according to claim 1, characterized in that: The deuterium donor reagent is selected from one or a combination of heavy water, deuterated methanol, deuterated ethanol, deuterated n-propanol, deuterated isopropanol, deuterated n-butanol, deuterated tert-butanol, and deuterated acetone.

4. The method for preparing the α-deuterated carboxylic acid derivative compound according to claim 1, characterized in that: The following steps are involved: Step 1: adding a carboxylic acid derivative compound and X zeolite into a reactor; Step 2: adding a deuterium donor reagent into a reactor and mixing to obtain a mixed solution; Step 3: Stir the mixed solution at a certain temperature for a certain period of time; Step 4: adding an organic solvent for extraction, drying and concentrating the organic phase, and purifying to obtain α-deuterated carboxylic acid derivative compounds.

5. The method for preparing the α-deuterated carboxylic acid derivative compound according to claim 1, characterized in that: The ratio of the molar amount of the carboxylic acid derivative compound to the mass of the X zeolite is 0.5:20 mmol / mg.

6. The method for preparing the α-deuterated carboxylic acid derivative compound according to claim 1, characterized in that: The reaction temperature is 80-150°C; the reaction time is 8-24h.

7. The method for preparing the α-deuterated carboxylic acid derivative compound according to claim 1, characterized in that: The molar ratio of silicon to aluminum in the X zeolite catalyst is 1.5 to 10.

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