13 Purification method of C octanoic acid and 13 C octanoic acid

Abstract

The present invention provides a 13 Purification method of C octanoic acid and 13 C octanoic acid, relates to the technical field of chemical drugs, the 13 The purification method of C octanoic acid comprises the following steps: 13 The crude product of C octanoic acid was dissolved, pH value adjusted and crystallized in sequence, and the crystals were obtained. 13 The present invention uses the recrystallization method to treat the crude product, decolorize and remove impurities, and can effectively remove 13 The impurities introduced during the synthesis of C octanoic acid are removed to improve the purity of the purified product. The purification method is cheap and easy to obtain, the processing process is simple and easy, no special equipment is required, and industrial production can be achieved. 13 The production and application of C octanoic acid are of great significance.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical drug purification, in particular to a 13 Purification method of C octanoic acid and 13 C octanoic acid. Background Art

[0002] Due to its non-invasive, non-radioactive, high sensitivity and good specificity, stable isotopes have become 13 Great progress has been made in the research of C-labeled diagnostic reagents. 13 The success of the urea breath test for the detection of Helicobacter pylori has 13 The C breath test is increasingly used in clinical diagnostic testing. As one of the most important digestive organs in the human body, the stomach plays an important role in the storage, digestion, and absorption of food. As an important indicator of the stomach, gastric emptying is related to nearly twenty diseases including gastric ulcers, gastric cancer, diabetes, hypothyroidism, Parkinson's disease, etc. Therefore, accurate detection of gastric emptying is of great significance for disease diagnosis. Gastric emptying tests generally include intubation, absorption tests, real-time ultrasound, radionuclide methods, etc. And the use of 13 Compared with the above methods, the use of C octanoic acid as a diagnostic reagent to detect gastric emptying using breath tests has obvious advantages such as being non-invasive and non-radioactive.

[0003] 13 C octanoic acid has broad application prospects as a diagnostic reagent for gastric emptying detection in breath tests. However, the crude product obtained from its synthesis contains a variety of impurities. The presence of impurities seriously affects the purity and abundance of the product, resulting in poor reliability of gastric emptying test results and difficulty meeting the requirements of breath tests. At the same time, impurities have certain toxicity and may cause harm to the human body during clinical use of drugs. Therefore, how to effectively remove them through purification methods is a key issue. 13 The impurities produced during the synthesis of C octanoic acid have become a problem that needs to be solved urgently.

[0004] Patent CN101417939B discloses a 13 A method for preparing C octanoic acid, wherein the crude octanoic acid is obtained by a Grignard reaction and then purified by acid-base reversal. Experimental verification shows that the octanoic acid obtained by this method still contains many impurities and the product purity is low.

[0005] 13 C octanoic acid is an oily liquid at room temperature. Common methods for purifying oily substances include distillation and column chromatography, but the purification effects are not ideal.

[0006] In view of this, the present invention is proposed. Summary of the Invention

[0007] One of the purposes of the present invention is to provide a13 The purification method of C octanoic acid is to solve at least one of the technical problems existing in the prior art. 13 The purification method of C octanoic acid can effectively remove 13 C Impurities in crude octanoic acid.

[0008] The second object of the present invention is to provide a 13 Purification method of C octanoic acid 13 C octanoic acid. Using the 13 Purification method of C octanoic acid 13 The yield and purity of C octanoic acid are higher.

[0009] In order to achieve the above-mentioned purpose of the present invention, the following technical solutions are adopted:

[0010] In a first aspect, the present invention provides a 13 The purification method of C octanoic acid comprises the following steps:

[0011] right 13 The crude product of C octanoic acid was dissolved, pH value adjusted and crystallized in sequence, and the crystals were obtained. 13 C octanoic acid finished product.

[0012] Furthermore, the solvent used for the dissolution includes at least one of n-hexane, acetonitrile, acetonitrile / water, acetone, ethyl acetate, cyclohexane, dichloromethane and ethanol.

[0013] Furthermore, the 13 The mass volume ratio of the crude C octanoic acid to the solvent is 1:(1-10).

[0014] Furthermore, the dissolution temperature is 10-40° C., and the dissolution time is 0.5-3 h.

[0015] Further, before adjusting the pH value, after dissolving 13 Add adsorbent to the crude solution of C octanoic acid, stir to decolorize, and then filter once;

[0016] Preferably, the 13 The mass ratio of the crude C octanoic acid to the adsorbent is 1:(0.01-0.20);

[0017] Preferably, the adsorbent comprises activated carbon;

[0018] Preferably, the stirring and decolorizing temperature is 10 to 40° C., and the stirring and decolorizing time is 1 to 3 hours.

[0019] Furthermore, after dissolution 13 C. Adjust the pH value of the crude octanoic acid solution to 2-4, preferably 2-3;

[0020] Preferably, an acid is used to adjust the pH;

[0021] Preferably, the acidic agent comprises at least one of formic acid, acetic acid, hydrochloric acid and sulfuric acid.

[0022] Furthermore, the crystallization includes cooling crystallization;

[0023] Preferably, the temperature of the cooling and crystallization is -10 to -40°C, and the time of the cooling and crystallization is 3 to 6 hours.

[0024] Furthermore, the 13 The purification method of C octanoic acid also comprises the following steps:

[0025] After the crystallization, secondary filtration is performed to obtain a solid product, and then the solvent in the solid product is removed;

[0026] Preferably, the secondary filtration includes reduced pressure filtration;

[0027] Preferably, the vacuum pressure of the reduced pressure filtration is -0.085 to -0.095 MPa;

[0028] Preferably, the instrument used for the secondary filtration is pre-cooled.

[0029] Furthermore, the removing of the solvent from the solid product comprises: concentrating the solid product under reduced pressure;

[0030] Preferably, the temperature of the reduced pressure concentration is 30 to 60° C., and the vacuum pressure of the reduced pressure concentration is -0.09 to -0.10 MPa.

[0031] In a second aspect, the present invention provides a 13 Purification method of C octanoic acid 13 C octanoic acid.

[0032] Compared with the prior art, the present invention has the following beneficial effects:

[0033] The present invention provides 13 The purification method of C octanoic acid is carried out by 13 C octanoic acid crude product was dissolved and the pH value of the solution was adjusted to make 13 C-caprylic acid tends to form a stable crystalline structure, which helps promote 13 The crystallization of C octanoic acid was realized by recrystallization. 13 Purification of crude C octanoic acid can effectively remove 13 C octanoic acid during the synthesis process to improve the purity of the purified product. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the specific embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0035] Figure 1 The embodiment of the present invention provides 13 C Liquid chromatogram of crude octanoic acid;

[0036] Figure 2 The purified product obtained from Example 1 of the present invention 13 Liquid chromatogram of C octanoic acid product. DETAILED DESCRIPTION

[0037] Unless otherwise defined herein, scientific and technical terms used in conjunction with the present invention shall have the meanings commonly understood by those of ordinary skill in the art. The meaning and scope of the terms should be clear; however, in the event of any potential ambiguity, the definitions provided herein take precedence over any dictionary or external definitions. In this application, the use of "or" means "and / or" unless otherwise stated. In addition, the use of the term "including" and other forms is non-limiting.

[0038] The following will clearly and completely describe the technical solutions of the present invention in conjunction with the embodiments. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0039] A first aspect of the present invention provides a 13 The purification method of C octanoic acid comprises the following steps:

[0040] right 13 The crude product of C octanoic acid was dissolved, pH value adjusted and crystallized in sequence, and the crystals were obtained. 13 C octanoic acid finished product.

[0041] 13 C octanoic acid is an oily liquid at room temperature, which is not easy to be purified by common solid purification methods such as recrystallization and beating. 13 C octanoic acid crude product was dissolved and the pH value of the solution was adjusted to make 13 C-caprylic acid tends to form a stable crystalline structure, which helps promote 13 The crystallization of C octanoic acid was realized by recrystallization. 13 Purification of crude C octanoic acid can effectively remove 13C octanoic acid during the synthesis process to improve the purity of the purified product.

[0042] In some preferred embodiments, the solvent used for dissolving includes at least one of n-hexane, acetonitrile, acetonitrile / water, acetone, ethyl acetate, cyclohexane, dichloromethane and ethanol.

[0043] In some preferred embodiments, the 13 The mass volume ratio of the crude C octanoic acid to the solvent is 1:(1-10), for example, it can be 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, etc.

[0044] The solvent selected by the present invention is purified by recrystallization 13 C octanoic acid provides a viable basis, different solvents and 13 C octanoic acid can form solutions with different solubility. By changing the type or proportion of solvent, the 13 C octanoic acid’s solubility in solution and crystallization behavior, thereby facilitating the separation of impurities.

[0045] In some preferred embodiments, the dissolution temperature is 10-40°C, for example, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, etc., and the dissolution time is 0.5-3h, for example, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, etc.

[0046] In some preferred embodiments, before adjusting the pH value, 13 Add activated carbon to the crude octanoic acid solution, stir to decolorize, and then filter once;

[0047] Preferably, the adsorbent comprises activated carbon;

[0048] In the present invention, activated carbon is added as an adsorbent to remove impurities in the solution. The use of activated carbon can not only help remove impurities insoluble in the target solvent, but also assist in improving the transparency of the solution, creating better conditions for subsequent recrystallization.

[0049] Preferably, the 13 The mass ratio of the crude C octanoic acid to the activated carbon is 1:(0.01-0.20), for example, 1:0.01, 1:0.15, 1:0.20, etc.;

[0050] Preferably, the stirring bleaching temperature is 10-40°C, for example, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, etc., and the stirring bleaching time is 1-3h, for example, 1h, 1.5h, 2h, 2.5h, 3h, etc.

[0051] In some preferred embodiments, the dissolved 13 The pH value of the crude octanoic acid solution is adjusted to 2 to 4, for example, 2, 3, and 4, etc., preferably 2 to 3, for example, 2 and 3, etc.;

[0052] In the present invention, by precisely adjusting the pH value of the solution to a specific range, it helps to promote 13 C octanoic acid crystals are precipitated. Under appropriate pH conditions, 13 C-octanoic acid tends to form a stable crystalline structure rather than remain in a liquid state, thereby improving the purification yield.

[0053] Preferably, an acid is used to adjust the pH;

[0054] Preferably, the acidic agent comprises at least one of formic acid, acetic acid, hydrochloric acid and sulfuric acid.

[0055] In some preferred embodiments, the crystallization comprises cooling crystallization;

[0056] Preferably, the temperature of the cooling crystallization is -10 to -40°C, for example, -10°C, -15°C, -20°C, -25°C, -30°C, -35°C, -40°C, etc., and the time of the cooling crystallization is 3 to 6h, for example, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, etc.

[0057] In the present invention, the crystallization operation is carried out under low temperature conditions to promote the target compound 13 C octanoic acid is crystallized with higher purity, which is beneficial to improving the purity of the target compound.

[0058] In some preferred embodiments, the 13 The purification method of C octanoic acid also comprises the following steps:

[0059] After the crystallization, secondary filtration is performed to obtain a solid product, and then the solvent in the solid product is removed;

[0060] Preferably, the secondary filtration includes reduced pressure filtration;

[0061] Preferably, the vacuum pressure of the reduced pressure filtration is -0.085 to -0.095 MPa;

[0062] Preferably, the instrument used for the secondary filtration is pre-cooled.

[0063] In the present invention, the instrument used for secondary filtration is preferably a Buchner funnel, and a pre-cooled Buchner funnel is used for reduced pressure filtration.

[0064] In some preferred embodiments, removing the solvent from the solid product comprises: concentrating the solid product under reduced pressure;

[0065] In the present invention, the reduced pressure concentration is adopted to avoid chemical reaction and decomposition possibly caused by high temperature, and ensure the recovery and reuse of the solvent, thereby improving the purity and yield of the final product.

[0066] Preferably, the temperature of the reduced pressure concentration is 30 to 60°C, for example, it can be 30°C, 35°C, 40°C, 45°C, 50°C, 55°C, 60°C, etc., and the vacuum pressure of the reduced pressure concentration is -0.09 to -0.10MPa, for example, it can be -0.09MPa, -0.095MPa, -0.10MPa, etc.

[0067] Furthermore, the 13 The purification method of C octanoic acid comprises the following steps:

[0068] (1) To 13 Add solvent to the crude C octanoic acid and stir until completely dissolved;

[0069] (2) Add activated carbon to the crude product solution, stir to decolorize, and filter;

[0070] (3) The pH value of the filtrate is adjusted with acid, the temperature is lowered to crystallize, and the filtrate is filtered under reduced pressure using a pre-cooled Buchner funnel;

[0071] (4) The solid obtained by filtration in (3) was concentrated under reduced pressure and the solvent was distilled off to obtain 13 C octanoic acid finished product.

[0072] The second aspect of the present invention provides a 13 Purification method of C octanoic acid 13 C octanoic acid.

[0073] In the present invention, by selecting a suitable solvent, controlling the amount of solvent added and the crystallization temperature, and adjusting the pH value of the system, the crude product is decolorized and purified by recrystallization, which can effectively remove 13 The impurities introduced during the synthesis of C octanoic acid are removed to improve the purity of the purified product. The purification method has cheap and easy reagents, simple purification method, simple and easy treatment process, mild conditions, no special equipment requirements, and can be industrialized for production. 13 The production and application of C octanoic acid are of great significance.

[0074] The present invention is further described below by way of examples. Unless otherwise specified, the materials in the examples were prepared according to existing methods or directly purchased from the market.

[0075] Examples of the present invention and comparative examples 13C octanoic acid crude product is obtained by 13 The product is prepared by the Grignard reaction of carbon dioxide with n-heptylmagnesium bromide, after the reaction is completed, hydrochloric acid or sulfuric acid is added to quench, the product is extracted, the base is adjusted with sodium hydroxide, and the acid is adjusted with hydrochloric acid to obtain 13 C octanoic acid crude product. Prepared by the above method 13 The liquid chromatogram of crude C octanoic acid is as follows Figure 1 shown.

[0076] In the following examples, the vacuum pressure used in the reduced pressure filtration was -0.085 to -0.095 MPa.

[0077] Example 1

[0078] This embodiment provides a 13 The purification method of C octanoic acid comprises the following steps:

[0079] To 50g 13 Add 150ml of n-hexane to the crude product of C octanoic acid and stir at room temperature (25°C) for 1h until completely dissolved. Add 2.5g of activated carbon and stir at 20-30°C for 2h to decolorize; filter, rinse the filter cake with 10ml of n-hexane, and combine the filtrates. Use acetic acid to adjust the pH value of the system to 2.5, cool to -20-30°C, stir and crystallize for 4h, and filter under reduced pressure using a pre-cooled Buchner funnel. The solid is quickly transferred to a 500ml single-necked bottle, concentrated under reduced pressure at 40°C and a vacuum pressure of -0.09-0.10MPa, and the solvent is evaporated to obtain 42.5g of colorless oil. 13 C octanoic acid finished product.

[0080] Purified by the above method 13 The liquid chromatogram of the finished product of C octanoic acid is as follows Figure 2 shown.

[0081] Example 2

[0082] This embodiment provides a 13 The purification method of C octanoic acid comprises the following steps:

[0083] To 50g 13 Add 100ml of acetonitrile to the crude product of C octanoic acid and stir at room temperature (25℃) for 2h until completely dissolved. Add 5.0g of activated carbon and stir at 20-30℃ for 1h to decolorize; filter, rinse the filter cake with 10ml of acetonitrile, and combine the filtrate. Adjust the pH value of the filtrate to 3.0 with formic acid, cool to -10-20℃, stir and crystallize for 3h, and filter under reduced pressure using a pre-cooled Buchner funnel. The solid is quickly transferred to a 500ml single-necked bottle, concentrated under reduced pressure at 50℃ and a vacuum pressure of -0.09-0.10MPa, and the solvent is evaporated to obtain 43.0g of colorless oil. 13 C octanoic acid finished product.

[0084] Example 3

[0085] This embodiment provides a 13 The purification method of C octanoic acid comprises the following steps:

[0086] To 50g 13 Add 100ml of acetone to the crude product of C octanoic acid and stir at room temperature (25℃) for 1h until completely dissolved. Add 2.5g of activated carbon and stir at 20-30℃ for 2h to decolorize; filter, rinse the filter cake with 10ml of acetone, and combine the filtrate. Use 1N hydrochloric acid to adjust the pH value of the filtrate to 3.5, cool to -20-30℃, stir and crystallize for 4h, and filter under reduced pressure using a pre-cooled Buchner funnel. The solid is quickly transferred to a 500ml single-necked bottle, concentrated under reduced pressure at 40℃ and a vacuum pressure of -0.09-0.10MPa, and the solvent is evaporated to obtain 42.3g of colorless oil. 13 C octanoic acid finished product.

[0087] Example 4

[0088] This embodiment provides a 13 The purification method of C octanoic acid comprises the following steps:

[0089] To 50g 13 Add 250ml of ethyl acetate to the crude product of C octanoic acid and stir at room temperature (25℃) for 2h until completely dissolved. Add 3.5g of activated carbon and stir at 30-40℃ for 1h to decolorize; filter, rinse the filter cake with 20ml of ethyl acetate, and combine the filtrate. Use 0.1N sulfuric acid to adjust the pH value of the system to 4.0, cool to -15--25℃, stir and crystallize for 3h, and filter under reduced pressure using a pre-cooled Buchner funnel. The solid is quickly transferred to a 500ml single-necked bottle, concentrated under reduced pressure at 50℃ and a vacuum pressure of -0.09--0.10MPa, and the solvent is evaporated to obtain 43.6g of colorless oil. 13 C octanoic acid finished product.

[0090] Example 5

[0091] This embodiment provides a 13 The purification method of C octanoic acid comprises the following steps:

[0092] To 100g 13Add 200 ml of acetonitrile / water mixed solvent (acetonitrile to water volume ratio 1:1) to the crude C octanoic acid, stir at room temperature (25°C) for 2 hours until completely dissolved. Add 5.0 g of activated carbon, stir and decolorize at 20-30°C for 1 hour; filter, rinse the filter cake with 20 ml of acetonitrile / water mixed solvent, and combine the filtrate. Use acetic acid to adjust the pH value of the filtrate to 2.5, cool to -20-30°C, stir and crystallize for 5 hours, and filter under reduced pressure using a pre-cooled Buchner funnel. The solid is quickly transferred to a 500 ml single-necked bottle, concentrated at 55°C and a vacuum pressure of -0.09-0.10 MPa, and the solvent is evaporated to obtain 88.2 g of colorless oil. 13 C octanoic acid finished product.

[0093] Example 6

[0094] This embodiment provides a 13 The purification method of C octanoic acid comprises the following steps:

[0095] To 100g 13 Add 150 ml of a mixed solvent of n-hexane / ethanol (volume ratio of n-hexane to ethanol is 1:1) to the crude product of C octanoic acid, and stir at room temperature (25°C) for 1 hour until completely dissolved. Add 6.0 g of activated carbon, stir and decolorize at 25-35°C for 1 hour; filter, rinse the filter cake with 15 ml of n-hexane, and combine the filtrate. Use 1N hydrochloric acid to adjust the pH value of the filtrate to 3.5, cool to -25-35°C, stir and crystallize for 6 hours, and filter under reduced pressure using a pre-cooled Buchner funnel. The solid is quickly transferred to a 500 ml single-necked bottle, concentrated under reduced pressure at 50°C and a vacuum pressure of -0.09-0.10 MPa, and the solvent is evaporated to obtain 83.4 g of a colorless oil. 13 C octanoic acid finished product.

[0096] Example 7

[0097] This embodiment provides a 13 The purification method of C octanoic acid is different from that of Example 5 in that the pH value of the system is adjusted to 2, and the rest is the same as that of Example 5.

[0098] Example 8

[0099] This embodiment provides a 13 The purification method of C octanoic acid is different from that of Example 5 in that the pH value of the system is adjusted to 3, and the rest is the same as that of Example 5.

[0100] Example 9

[0101] This embodiment provides a 13 The purification method of C octanoic acid is different from that of Example 5 in that the pH value of the system is adjusted to 3.5, and the rest is the same as that of Example 5.

[0102] Example 10

[0103] This embodiment provides a 13 The purification method of C octanoic acid is different from that of Example 5 in that:

[0104] 100 ml of acetonitrile / water mixed solvent was stirred at 10 °C for 3 h until completely dissolved;

[0105] Add 1.0 g of activated carbon and stir at 10-20°C for 3 h to decolorize; filter, rinse the filter cake with 10 ml of acetonitrile / water mixed solvent, and combine the filtrates;

[0106] After adjusting the pH, cool down to -30~-40℃;

[0107] The mixture was concentrated under reduced pressure at 30°C to give 88.5 g of a colorless oil. 13 C octanoic acid finished product;

[0108] The remaining steps are consistent with Example 5.

[0109] Example 11

[0110] This embodiment provides a 13 The purification method of C octanoic acid is different from that of Example 10 in that:

[0111] 1000 ml of acetonitrile / water mixed solvent was stirred at 40 °C for 0.5 h until completely dissolved;

[0112] Add 20 g of activated carbon; rinse the filter cake with 100 ml of acetonitrile / water mixed solvent and combine the filtrates;

[0113] The mixture was concentrated under reduced pressure at 60°C to give 83.2 g of a colorless oil. 13 C octanoic acid finished product;

[0114] The remaining steps are consistent with Example 10.

[0115] Example 12

[0116] This embodiment provides a 13 The purification method of C octanoic acid is different from that of Example 5 in that the pH value of the system is adjusted to 1.5, and the rest is the same as that of Example 5.

[0117] Example 13

[0118] This embodiment provides a 13 The purification method of C octanoic acid is different from that of Example 5 in that the pH value of the system is adjusted to 4.5, and the rest is the same as that of Example 5.

[0119] Example 14

[0120] This embodiment provides a 13The purification method of C octanoic acid is the same as that of Example 5 except that the amount of the acetonitrile / water mixed solvent is 50 ml. The rest is the same as that of Example 5.

[0121] Example 15

[0122] This embodiment provides a 13 The purification method of C octanoic acid is the same as that of Example 5 except that the amount of the acetonitrile / water mixed solvent is 1050 ml. The rest is the same as that of Example 5.

[0123] Example 16

[0124] This embodiment provides a 13 The purification method of C octanoic acid is different from that of Example 5 in that after adjusting the pH value of the solution, the temperature is lowered to -5°C. The rest is the same as that of Example 5.

[0125] Example 17

[0126] This embodiment provides a 13 The purification method of C octanoic acid is different from that of Example 5 in that after adjusting the pH value of the solution, the temperature is lowered to -45°C. The rest is the same as that of Example 5.

[0127] Comparative Example 1

[0128] This comparative example provides a 13 The purification method of C octanoic acid is different from that of Example 5 in that:

[0129] No pH adjustment operation was performed, and the remaining steps were consistent with Example 5.

[0130] Comparative Example 2

[0131] This comparative example provides a 13 The purification method of C octanoic acid is to purify it by distillation. The specific steps are as follows: take 100g 13 C octanoic acid crude product was put into a 250ml distillation flask, stirred and heated, and distilled under reduced pressure, controlling the vacuum pressure to ≤-0.095MPa. The distillate with a temperature below 120℃ was collected as the front fraction, and the distillate with a temperature between 120℃ and 140℃ was collected as the product, and a total of 70.5g of light yellow oil was obtained. 13 C octanoic acid finished product.

[0132] Comparative Example 3 This comparative example provides a 13 The purification method of C octanoic acid is to purify it by column chromatography. The specific steps are as follows: take 50.0g 13The crude product of C octanoic acid was added to a chromatography column filled with 200-300 mesh silica gel and eluted with ethyl acetate / petroleum ether at a gradient ratio of 1:10, 1:8, 1:6, 1:4, and 1:2 (volume ratio). The eluate was monitored by TLC spot plate and the high-purity eluate was collected. The eluate was concentrated under reduced pressure at 45-50°C to obtain 30.2 g of colorless oil. 13 C octanoic acid finished product.

[0133] Test Case

[0134] Test sample: purified using the purification method of Example 1-17 13 C octanoic acid and the comparative example 1-3 purification method were purified 13 C octanoic acid.

[0135] The yield of the test sample was calculated and the purity was tested, and the obtained data are shown in Table 1 below.

[0136] Table 1

[0137] Yield (%) purity(%) Example 1 85.0 100.00 Example 2 86.0 99.95 Example 3 84.6 99.92 Example 4 87.2 99.93 Example 5 88.2 100.00 Example 6 83.4 100.00 Example 7 87.6 100.00 Example 8 87.5 100.00 Example 9 86.1 99.96 Example 10 88.5 99.91 Example 11 83.2 100.00 Example 12 82.5 99.86 Example 13 81.6 99.90 Example 14 88.4 96.32 Example 15 81.2 99.99 Example 16 80.6 99.95 Example 17 88.3 98.20 Comparative Example 1 78.6 98.10 Comparative Example 2 70.5 95.68 Comparative Example 3 60.4 94.50

[0138] As can be seen from the data in the table, the data results of Example 5, Example 7, Example 8 and Example 9 are compared, and the 13 When the pH value of the crude C octanoic acid solution is adjusted to 2-3, the yield of the product is significantly improved; and the yield and purity of the product prepared using the specific parameter range of the embodiment of the present invention are significantly improved.

[0139] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A 13 The purification method of C octanoic acid is characterized in that The following steps are involved: right 13 The crude product of C octanoic acid was dissolved, pH value adjusted and crystallized in sequence, and the crystals were obtained. 13 C octanoic acid finished product; The solvent used for dissolving includes at least one of n-hexane, acetonitrile, acetonitrile / water, acetone, ethyl acetate, cyclohexane, dichloromethane and ethanol; described 13 The mass volume ratio of crude C octanoic acid to solvent is 1:(1~10); After dissolution 13 Adjust the pH value of the crude octanoic acid solution to 2-4; The crystallization includes cooling crystallization; the temperature of the cooling crystallization is -10~-40℃.

2. according to claim 1 13 The purification method of C octanoic acid is characterized in that The dissolution temperature is 10-40° C., and the dissolution time is 0.5-3 h.

3. according to claim 1 13 The purification method of C octanoic acid is characterized in that Before adjusting the pH value, after dissolution 13 Add adsorbent to the crude solution of C octanoic acid, stir to decolorize, and then filter once.

4. according to claim 3 13 The purification method of C octanoic acid is characterized in that described 13 The mass ratio of the crude C octanoic acid to the adsorbent is 1:(0.01~0.20).

5. according to claim 3 13 The purification method of C octanoic acid is characterized in that The adsorbent includes activated carbon.

6. according to claim 3 13 The purification method of C octanoic acid is characterized in that The stirring and decolorizing temperature is 10-40° C., and the stirring and decolorizing time is 1-3 hours.

7. according to claim 1 13 The purification method of C octanoic acid is characterized in that After dissolution 13 Adjust the pH value of the crude C octanoic acid solution to 2~3.

8. according to claim 1 13 The purification method of C octanoic acid is characterized in that Use an acid to adjust the pH.

9. according to claim 8 13 The purification method of C octanoic acid is characterized in that The acidic agent includes at least one of formic acid, acetic acid, hydrochloric acid and sulfuric acid.

10. according to claim 1 13 The purification method of C octanoic acid is characterized in that The cooling and crystallization time is 3 to 6 hours.

11. according to claim 1 13 The purification method of C octanoic acid is characterized in that described 13 The purification method of C octanoic acid also comprises the following steps: After the crystallization, secondary filtration is performed to obtain a solid product, and then the solvent in the solid product is removed.

12. The method according to claim 11 13 The purification method of C octanoic acid is characterized in that The secondary filtration includes reduced pressure filtration.

13. The method according to claim 12 13 The purification method of C octanoic acid is characterized in that The vacuum pressure of the reduced pressure filtration is -0.085~-0.095MPa.

14. The method according to claim 11 13 The purification method of C octanoic acid is characterized in that The instrument used for the secondary filtration is pre-cooled.

15. The method according to claim 11 13 The purification method of C octanoic acid is characterized in that The removing of the solvent from the solid product comprises: concentrating the solid product under reduced pressure.

16. The method according to claim 11 13 The purification method of C octanoic acid is characterized in that The temperature of the reduced pressure concentration is 30~60°C, and the vacuum pressure of the reduced pressure concentration is -0.09~-0.10MPa.

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