CN116836054B - Preparation method of tetradecanoic acid crystal form, crystal form and application thereof - Google Patents
Preparation method of tetradecanoic acid crystal form, crystal form and application thereof Download PDFInfo
- Publication number
- CN116836054B CN116836054B CN202310893862.0A CN202310893862A CN116836054B CN 116836054 B CN116836054 B CN 116836054B CN 202310893862 A CN202310893862 A CN 202310893862A CN 116836054 B CN116836054 B CN 116836054B
- Authority
- CN
- China
- Prior art keywords
- tetradecanoic acid
- crystal form
- acid
- tetradecanoic
- toluene
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 title claims abstract description 209
- 239000013078 crystal Substances 0.000 title claims abstract description 44
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 64
- 238000000034 method Methods 0.000 claims abstract description 23
- 238000001035 drying Methods 0.000 claims abstract description 18
- 238000001816 cooling Methods 0.000 claims abstract description 16
- 238000001914 filtration Methods 0.000 claims abstract description 14
- 238000010438 heat treatment Methods 0.000 claims abstract description 14
- 238000003756 stirring Methods 0.000 claims abstract description 14
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 5
- 230000005855 radiation Effects 0.000 claims description 3
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 abstract description 28
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 abstract description 24
- 239000012535 impurity Substances 0.000 abstract description 21
- 239000000047 product Substances 0.000 abstract description 19
- 238000001953 recrystallisation Methods 0.000 abstract description 18
- 235000021314 Palmitic acid Nutrition 0.000 abstract description 14
- 190000032366 miboplatin Chemical compound 0.000 abstract description 12
- 229950002777 miboplatin Drugs 0.000 abstract description 12
- YAQXGBBDJYBXKL-UHFFFAOYSA-N iron(2+);1,10-phenanthroline;dicyanide Chemical compound [Fe+2].N#[C-].N#[C-].C1=CN=C2C3=NC=CC=C3C=CC2=C1.C1=CN=C2C3=NC=CC=C3C=CC2=C1 YAQXGBBDJYBXKL-UHFFFAOYSA-N 0.000 abstract description 11
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 abstract description 11
- 239000003814 drug Substances 0.000 abstract description 6
- 239000007858 starting material Substances 0.000 abstract description 5
- 239000012043 crude product Substances 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- 239000002904 solvent Substances 0.000 description 19
- 230000000052 comparative effect Effects 0.000 description 12
- 238000002425 crystallisation Methods 0.000 description 11
- 230000008025 crystallization Effects 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- LRCTTYSATZVTRI-UHFFFAOYSA-L cyclohexane-1,2-diamine;platinum(4+);tetradecanoate Chemical compound [Pt+4].NC1CCCCC1N.CCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCC([O-])=O LRCTTYSATZVTRI-UHFFFAOYSA-L 0.000 description 3
- MHYCRLGKOZWVEF-UHFFFAOYSA-N ethyl acetate;hydrate Chemical compound O.CCOC(C)=O MHYCRLGKOZWVEF-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229950004962 miriplatin Drugs 0.000 description 3
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 3
- 238000007670 refining Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229940045845 sodium myristate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- JUQGWKYSEXPRGL-UHFFFAOYSA-M sodium;tetradecanoate Chemical compound [Na+].CCCCCCCCCCCCCC([O-])=O JUQGWKYSEXPRGL-UHFFFAOYSA-M 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
- C07C53/126—Acids containing more than four carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System compounds of the platinum group
- C07F15/0086—Platinum compounds
- C07F15/0093—Platinum compounds without a metal-carbon linkage
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Abstract
The invention relates to the technical field of chemical pharmacy, in particular to a preparation method of a tetradecanoic acid crystal form, and a crystal form and application thereof. The preparation method of the tetradecanoic acid crystal form comprises the following steps: adding the crude tetradecanoic acid into toluene solvent, stirring, heating to dissolve, cooling, crystallizing, filtering and drying to obtain the product. According to the invention, the tetradecanoic acid crystal form can be obtained by recrystallizing the crude product of the tetradecanoic acid through toluene, and impurities of homologs such as dodecanoic acid, pentadecanoic acid and hexadecanoic acid in the tetradecanoic acid can be effectively removed, the single impurity content in the tetradecanoic acid crystal form obtained by recrystallization is lower than 0.05%, the quality standard is met, the single impurity content in the miboplatin raw material medicine can be ensured to be less than 0.1%, and the miboplatin raw material medicine can be used as a miboplatin starting material. The recrystallization method provided by the invention avoids the generation of impurities in the synthesis of the miboplatin.
Description
Technical Field
The invention relates to the technical field of chemical pharmacy, in particular to a preparation method of a tetradecanoic acid crystal form, and a crystal form and application thereof.
Background
Tetradecanoic acid is a key starting material for synthesizing a miboplatin bulk drug, and the quality of the tetradecanoic acid is very important to the quality of a miboplatin finished product. Commercially available tetradecanoic acid often contains small amounts of the dodecanoic acid to hexadecanoic acid equivalent, with the contents of dodecanoic acid, pentadecanoic acid, and hexadecanoic acid being relatively high. The above homolog has a similar structure to tetradecanoic acid, and the physical properties of impurities generated by the reaction are similar to those of the miriplatin, and the impurities are difficult to remove in the refining process of the miriplatin, so that the quality of the miriplatin is greatly influenced.
According to the report in the literature, when the content of single impurities of the homologs of dodecanoic acid, pentadecanoic acid and hexadecanoic acid or sodium salt thereof in the tetradecanoic acid is not more than 0.05%, the single impurities in the miboplatin bulk drug can be ensured to be less than 0.1%. The purification method reported in the prior literature adopts ethyl acetate and water to refine sodium myristate, and has better removal effect on dodecanoic acid, but has poorer removal effect on pentadecanoic acid and hexadecanoic acid, and particularly has almost no removal effect on hexadecanoic acid, so that the hexadecanoic acid is difficult to control within 0.05%, and the tetradecanoic acid crystal form meeting the quality standard is difficult to prepare.
Therefore, it is necessary to find a method for producing tetradecanoic acid which does not contain impurities of the equivalent systems of dodecanoic acid, pentadecanoic acid and hexadecanoic acid.
Disclosure of Invention
Aiming at the technical problems, the invention provides a preparation method of a tetradecanoic acid crystal form, and the crystal form and application thereof. According to the preparation method of the tetradecanoic acid crystal form, the tetradecanoic acid crystal form can be obtained by recrystallizing a crude product of the tetradecanoic acid through toluene, and homolog impurities such as dodecanoic acid, pentadecanoic acid and hexadecanoic acid in the tetradecanoic acid can be effectively removed.
In order to solve the technical problems, the invention adopts the following technical scheme:
in a first aspect, the present invention provides a method for preparing a crystalline form of tetradecanoic acid, comprising the steps of: adding the crude tetradecanoic acid into toluene solvent, stirring, heating to dissolve, cooling, crystallizing, filtering and drying to obtain the product.
According to the invention, the tetradecanoic acid crystal form can be obtained by recrystallizing the crude product of the tetradecanoic acid through toluene, and impurities of homologs such as dodecanoic acid, pentadecanoic acid and hexadecanoic acid in the tetradecanoic acid can be effectively removed, the single impurity content in the tetradecanoic acid crystal form obtained by recrystallization is lower than 0.05%, the quality standard is met, the single impurity content in the miboplatin raw material medicine can be ensured to be less than 0.1%, and the miboplatin raw material medicine can be used as a miboplatin starting material.
Alternatively, the mass to volume ratio of tetradecanoic acid to toluene is 1:5-10.
When the mass-volume ratio of the tetradecanoic acid to the toluene is 1:5-10, the single impurities of the equivalent systems of the dodecanoic acid, the pentadecanoic acid and the hexadecanoic acid can be controlled to be lower than 0.05 percent so as to meet the requirement of the obtained tetradecanoic acid crystal form as a miboplatin starting material.
When the mass-volume ratio of the tetradecanoic acid to the toluene is more than 1:10, the impurity removing effect is better, but the lower the yield of the tetradecanoic acid product is, the production cost is increased. When the mass-to-volume ratio of tetradecanoic acid to toluene is less than 1:5, the higher the yield of tetradecanoic acid product, but the poorer the removal effect of impurities. Therefore, the mass-volume ratio of the tetradecanoic acid to the toluene is selected to be 1:5-10 in comprehensive consideration.
Optionally, the temperature is raised to 55-60 ℃.
The above-mentioned temperature rise of the present invention can well dissolve tetradecanoic acid and its homolog impurity.
Optionally, the temperature is slowly reduced to 10-15 ℃, and the temperature reduction rate is 0.5 ℃/min.
The above temperature reduction temperature of the invention is beneficial to the recrystallization of the tetradecanoic acid, and the tetradecanoic acid crystal form meeting the quality standard is obtained.
Optionally, the drying temperature is 50-55 ℃ and the drying time is 8-9h.
In a second aspect, the present invention also provides the above-mentioned tetradecanoic acid crystal form, wherein the Cu-ka radiation is used, the X-ray powder diffraction expressed in terms of 2θ is used, and the X-RPD has characteristic diffraction peaks at 2θ=4.9±0.2°, 12.0±0.2°, 12.9±0.2°, 19.2±0.2°, 19.7±0.2°, 23.4±0.2°, 23.6±0.2°, 24.1±0.2°, 24.5±0.2° and 25.9±0.2°.
The tetradecanoic acid crystal form has stable structure, is granular, is easy to filter when being treated after recrystallization, does not wrap a solvent, and has high crystal form purity.
Preferably, the X-ray powder diffraction expressed in terms of 2θ has characteristic diffraction peaks at 2θ=4.9±0.2°, 7.2±0.2°, 9.0±0.2° 12.0±0.2°, 12.9±0.2°, 15.3±0.2°, 19.2±0.2°, 19.7±0.2°, 21.4±0.2°, 23.4±0.2°, 23.6±0.2°, 24.1±0.2°, 24.5±0.2°, 25.9±0.2°, 28.0±0.2° and 30.9±0.2°.
Preferably, the X-RPD has characteristic diffraction peaks at 2θ=4.9±0.2°, 7.2±0.2°, 7.6±0.2°, 9.0±0.2°, 9.7±0.2°, 12.0±0.2°, 12.9±0.2°, 13.3±0.2°, 15.3±0.2°, 16.6±0.2°, 19.2±0.2°, 19.7±0.2°, 21.4±0.2°, 22.0±0.2°, 23.4±0.2°, 23.6±0.2°, 24.1±0.2°, 24.5±0.2°, 25.9±0.2°, 28.0.2±0.2°, 29.1±0.2°, 30.9±0.2°, 31.3±0.2°, 34.1±0.2°, and 34.6±0.2°.2.
In a third aspect, the invention also provides a tetradecanoic acid crystal form obtained by the preparation method of the tetradecanoic acid crystal form or application of the tetradecanoic acid crystal form in preparation of the miboplatin.
Drawings
FIG. 1 is an XRD spectrum of the tetradecanoic acid crystal form obtained in example 1 of the present invention;
FIG. 2 is an XRD integral of the crystalline form of tetradecanoic acid obtained in example 1 of the present invention.
Detailed Description
The present invention will be described in further detail with reference to specific embodiments in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
Example 1
The embodiment of the invention provides a recrystallization method of tetradecanoic acid, which comprises the following steps: dissolving a crude tetradecanoic acid product into a toluene solvent, wherein the mass-volume ratio of the tetradecanoic acid to the toluene is 1:10; heating to 55 ℃, stirring and dissolving until a toluene solvent system is clarified, slowly cooling to 10 ℃ for crystallization, filtering, and drying at 50 ℃ for 8 hours to obtain the recrystallized tetradecanoic acid crystal form.
Example 2
The embodiment of the invention provides a recrystallization method of tetradecanoic acid, which comprises the following steps: dissolving a crude tetradecanoic acid product into a toluene solvent, wherein the mass-volume ratio of the tetradecanoic acid to the toluene is 1:8; heating to 58 ℃, stirring and dissolving until a toluene solvent system is clarified, slowly cooling to 12 ℃ for crystallization, filtering, and drying at 55 ℃ for 9 hours to obtain the recrystallized tetradecanoic acid crystal form.
Example 3
The embodiment of the invention provides a recrystallization method of tetradecanoic acid, which comprises the following steps: dissolving a crude tetradecanoic acid product into a toluene solvent, wherein the mass-volume ratio of the tetradecanoic acid to the toluene is 1:5; heating to 60 ℃, stirring and dissolving until a toluene solvent system is clarified, slowly cooling to 15 ℃ for crystallization, filtering, and drying at 50 ℃ for 8 hours to obtain the recrystallized tetradecanoic acid crystal form.
Comparative example 1
The embodiment of the invention provides a recrystallization method of tetradecanoic acid, which comprises the following steps: dissolving a crude tetradecanoic acid product into an ethyl acetate water solvent, wherein the mass volume ratio of the tetradecanoic acid to the ethyl acetate water solvent is 1:10, and the volume ratio of the ethyl acetate to the water is 1:1; heating to 55 ℃, stirring and dissolving until an ethyl acetate water solvent system is clarified, slowly cooling to 10 ℃ for crystallization, filtering, and drying at 50 ℃ for 8 hours to obtain the recrystallized tetradecanoic acid crystal form.
Comparative example 2
The embodiment of the invention provides a recrystallization method of tetradecanoic acid, which comprises the following steps: dissolving a crude tetradecanoic acid product into an absolute ethyl alcohol solvent, wherein the mass-volume ratio of the tetradecanoic acid to the absolute ethyl alcohol solvent is 1:10; heating to 55 ℃, stirring and dissolving until the absolute ethyl alcohol solvent system is clear, slowly cooling to 10 ℃ for crystallization, filtering, and drying at 50 ℃ for 8 hours to obtain the recrystallized tetradecanoic acid crystal form.
Comparative example 3
The embodiment of the invention provides a recrystallization method of tetradecanoic acid, which comprises the following steps: dissolving a crude tetradecanoic acid product into a normal hexane solvent, wherein the mass-volume ratio of the tetradecanoic acid to the normal hexane is 1:10; heating to 55 ℃, stirring and dissolving until the n-hexane solvent system is clear, slowly cooling to 10 ℃ for crystallization, filtering, and drying at 50 ℃ for 8 hours to obtain the recrystallized tetradecanoic acid crystal form.
Comparative example 4
The embodiment of the invention provides a recrystallization method of tetradecanoic acid, which comprises the following steps: dissolving a crude tetradecanoic acid product into an acetone solvent, wherein the mass-volume ratio of the tetradecanoic acid to the acetone is 1:10; heating to 55 ℃, stirring and dissolving until an acetone solvent system is clarified, slowly cooling to 10 ℃ for crystallization, filtering, and drying at 50 ℃ for 8 hours to obtain the recrystallized tetradecanoic acid crystal form.
Comparative example 5
The embodiment of the invention provides a recrystallization method of tetradecanoic acid, which comprises the following steps: dissolving a crude tetradecanoic acid product into an acetone-water solvent, wherein the mass volume ratio of the tetradecanoic acid to the acetone-water solvent is 1:10, and the volume ratio of the acetone to the water is 1:1; heating to 55 ℃, stirring and dissolving until an acetone-water solvent system is clarified, slowly cooling to 10 ℃ for crystallization, filtering, and drying at 50 ℃ for 8 hours to obtain the recrystallized tetradecanoic acid crystal form.
Comparative example 6
The embodiment of the invention provides a recrystallization method of tetradecanoic acid, which comprises the following steps: dissolving a crude tetradecanoic acid product into a methanol solvent, wherein the mass-volume ratio of the tetradecanoic acid to the methanol solvent is 1:10; heating to 55 ℃, stirring and dissolving until a methanol solvent system is clarified, slowly cooling to 10 ℃ for crystallization, filtering, and drying at 50 ℃ for 8 hours to obtain the recrystallized tetradecanoic acid crystal form.
Comparative example 7
The embodiment of the invention provides a recrystallization method of tetradecanoic acid, which comprises the following steps: dissolving a crude tetradecanoic acid product into a toluene solvent, wherein the mass-volume ratio of the tetradecanoic acid to the toluene is 1:15; heating to 55 ℃, stirring and dissolving until a toluene solvent system is clarified, slowly cooling to 10 ℃ for crystallization, filtering, and drying at 50 ℃ for 8 hours to obtain the recrystallized tetradecanoic acid crystal form.
Comparative example 8
The embodiment of the invention provides a recrystallization method of tetradecanoic acid, which comprises the following steps: dissolving a crude tetradecanoic acid product into a toluene solvent, wherein the mass-volume ratio of the tetradecanoic acid to the toluene is 1:2; heating to 55 ℃, stirring and dissolving until a toluene solvent system is clarified, slowly cooling to 10 ℃ for crystallization, filtering, and drying at 50 ℃ for 8 hours to obtain the recrystallized tetradecanoic acid crystal form.
Verification example 1
The results of examination of the methods for refining tetradecanoic acid of examples 1 to 3 and comparative examples 1 to 8 are shown in Table 1.
Table 1 examination results of the method for refining tetradecanoic acid
From Table 1, it is clear that in examples 1-3, the content of impurities of equivalent substances of dodecanoic acid, pentadecanoic acid and hexadecanoic acid in tetradecanoic acid can be controlled to be less than or equal to 0.05% by recrystallizing a crude product of tetradecanoic acid from toluene with 5-10 times of the mass of the tetradecanoic acid, and the dodecanoic acid, the pentadecanoic acid and the hexadecanoic acid in the tetradecanoic acid can be effectively removed to obtain a tetradecanoic acid crystal form meeting the quality standard, the product yield is higher, the purity can reach more than 99.8%, and the requirement of a midlatinum starting material is met.
The solvents in comparative examples 1 to 6 all had a certain removal effect on dodecanoic acid, but the removal ability was poor on pentadecanoic acid and hexadecanoic acid, and the requirement that the single impurity was controlled to be less than or equal to 0.05% was not satisfied.
The experimental result of comparative example 7 shows that the higher the mass-to-volume ratio (1:15) of tetradecanoic acid to toluene, the better the impurity removal effect, but the lower the product yield, the higher the production cost. Comparative example 8 the experimental results show that the smaller the mass to volume ratio of tetradecanoic acid to toluene (1:2), the higher the product yield, but the poorer the impurity removal effect.
Verification example 2
XRD analysis was performed on the tetradecanoic acid crystal form obtained by recrystallization of example 1, and the results are shown in FIG. 1.
FIG. 1 is an XRD spectrum of the tetradecanoic acid crystal form obtained in example 1 of the present invention;
FIG. 2 is an XRD integral of the crystalline form of tetradecanoic acid obtained in example 1 of the present invention.
As can be seen from FIGS. 1 and 2, cu-K alpha radiation is used at 2 θ X-ray powder diffraction X-RPD of angle expression is 2 θ The diffraction peaks are characteristic at the angles of=4.9±0.2°, 7.2±0.2°, 7.6±0.2°, 9.0±0.2°, 9.7±0.2°, 12.0±0.2°, 12.9±0.2°, 13.3±0.2°, 15.3±0.2°, 16.6±0.2°, 19.2±0.2°, 19.7±0.2°, 21.4±0.2°, 22.0±0.2°, 23.4±0.2°, 23.6±0.2°, 24.1±0.2°, 24.5±0.2°, 25.9±0.2°, 28.0.2±0.2°, 29.1±0.2°, 30.9±0.2°, 31.3±0.2°, 34.1±0.2°, and 34.6±0.2°.
The tetradecanoic acid crystal form obtained by the invention has stable structure, is granular, is easy to filter when being treated after recrystallization, does not wrap a solvent, and has high crystal form purity.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, or alternatives falling within the spirit and principles of the invention.
Claims (7)
1. The preparation method of the tetradecanoic acid crystal form is characterized by comprising the following steps: adding the crude tetradecanoic acid into toluene solvent, stirring, heating to dissolve, cooling, crystallizing, filtering and drying to obtain the product;
the mass volume ratio of the tetradecanoic acid to the toluene is 1:5-10.
2. The process for the preparation of crystalline tetradecanoic acid according to claim 1, characterized in that the temperature is raised to 55-60 ℃.
3. The method for preparing a crystalline form of tetradecanoic acid according to claim 1, wherein the cooling is slow to 10-15 ℃, and the cooling rate is 0.5 ℃ per minute.
4. The method for preparing a crystalline form of tetradecanoic acid according to claim 1, wherein the drying temperature is 50-55 ℃ and the drying time is 8-9h.
5. The method of preparing crystalline form of tetradecanoic acid according to claim 1, wherein the crystalline form uses Cu-ka radiation, X-ray powder diffraction expressed in terms of 2Θ, and X-RPD has characteristic diffraction peaks at 2Θ = 4.9 ± 0.2 °, 12.0 ± 0.2 °, 12.9 ± 0.2 °, 19.2 ± 0.2 °, 19.7 ± 0.2 °, 23.4 ± 0.2 °, 23.6 ± 0.2 °, 24.1 ± 0.2 °, 24.5 ± 0.2 ° and 25.9 ± 0.2 °.
6. The method for preparing a crystalline form of tetradecanoic acid according to claim 5, wherein the X-ray powder diffraction expressed in terms of 2Θ includes characteristic diffraction peaks at 2Θ = 4.9 ± 0.2 °, 7.2 ± 0.2 °, 9.0 ± 0.2 ° 12.0 ± 0.2 °, 12.9 ± 0.2 °, 15.3 ± 0.2 °, 19.2 ± 0.2 °, 19.7 ± 0.2 °, 21.4 ± 0.2 °, 23.4 ± 0.2 °, 23.6 ± 0.2 °, 24.1 ± 0.2 °, 24.5 ± 0.2 °, 25.9 ± 0.2 °, 28.0 ± 0.2 ° and 30.9 ± 0.2 °.
7. The method of preparing a crystalline form of tetradecanoic acid according to claim 5 or 6, wherein X-RPD has diffraction peaks at 2Θ = 4.9±0.2 °, 7.2±0.2 °, 7.6±0.2 °, 9.0±0.2 °, 9.7±0.2 °, 12.0±0.2 °, 12.9±0.2 °, 13.3±0.2 °, 15.3±0.2 °, 16.6±0.2 °, 19.2±0.2 °, 19.7±0.2 °, 21.4±0.2 °, 22.0±0.2 °, 23.4±0.2 °, 23.6±0.2 °, 24.1±0.2 °, 24.5±0.2 °, 25.9±0.2 °, 28.0±0.2 °, 29.1±0.2 °, 30.9±0.2 °, 31.3.3±0.2°, 34.1±0.2°, and 34.6±0.2 °.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310893862.0A CN116836054B (en) | 2023-07-20 | 2023-07-20 | Preparation method of tetradecanoic acid crystal form, crystal form and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310893862.0A CN116836054B (en) | 2023-07-20 | 2023-07-20 | Preparation method of tetradecanoic acid crystal form, crystal form and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN116836054A CN116836054A (en) | 2023-10-03 |
| CN116836054B true CN116836054B (en) | 2024-03-08 |
Family
ID=88174254
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310893862.0A Active CN116836054B (en) | 2023-07-20 | 2023-07-20 | Preparation method of tetradecanoic acid crystal form, crystal form and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116836054B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103012100A (en) * | 2012-12-28 | 2013-04-03 | 李赛荣 | Myristic acid purification method |
| CN104119387A (en) * | 2013-04-24 | 2014-10-29 | 正大天晴药业集团股份有限公司 | Preparation method for miriplatin |
| CN109021019A (en) * | 2017-06-09 | 2018-12-18 | 鲁南制药集团股份有限公司 | A kind of preparation method of Miboplatin |
-
2023
- 2023-07-20 CN CN202310893862.0A patent/CN116836054B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103012100A (en) * | 2012-12-28 | 2013-04-03 | 李赛荣 | Myristic acid purification method |
| CN104119387A (en) * | 2013-04-24 | 2014-10-29 | 正大天晴药业集团股份有限公司 | Preparation method for miriplatin |
| CN109021019A (en) * | 2017-06-09 | 2018-12-18 | 鲁南制药集团股份有限公司 | A kind of preparation method of Miboplatin |
Non-Patent Citations (4)
| Title |
|---|
| "高压固液气相平衡及结晶行为的研究";花丹;厦门大学硕士学位论文;第63-64页第5.3.1.2XRD分析 * |
| Phase transformation in the C form of myristic-acid crystals and DFT calculations;J.R.S. Miranda，et al.;Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy;第208卷;第97-108页 * |
| 米铂的合成工艺改进;褚延军;王春燕;刘戈;提文利;张贵民;;中国医药工业杂志(04);第484-486、531页，第485页图1 * |
| 花丹."高压固液气相平衡及结晶行为的研究".厦门大学硕士学位论文.2013,第63-64页第5.3.1.2XRD分析. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN116836054A (en) | 2023-10-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2022176979A5 (en) | ||
| JPS6245576A (en) | Production of stable derivative of tracemide and diuretic containing stable torasemide | |
| CN104513256B (en) | A kind of preparation method of Cefditoren pivoxil Cephalosporins | |
| EP3241837A1 (en) | Method for preparing sofosbuvir crystal form-6 | |
| JPH0377199B2 (en) | ||
| EP2621889B1 (en) | Process for making fingolimod hydrochloride crystals | |
| CN116836054B (en) | Preparation method of tetradecanoic acid crystal form, crystal form and application thereof | |
| CN107531744B (en) | Novel crystal form of obeticholic acid and preparation method thereof | |
| CN102584693B (en) | Preparation method for high purity 2-chlorine-3-aminopyridine hydrochloride | |
| CN112028896A (en) | Novel crystal form of acatinib and preparation method thereof | |
| EP1673359B1 (en) | Process for the preparation of crystalline forms of orlistat | |
| WO2017167949A1 (en) | Crystalline forms of bilastine | |
| KR101704563B1 (en) | Method and apparatus for preparation of lactide using lactide purification process | |
| JP3963613B2 (en) | Method for producing hydroxyphenylcyclohexanone derivative | |
| CN110845407B (en) | Preparation method of chloroquinate crystal | |
| CN110229087B (en) | Purification method of (1R,2R) -1- [ (4-methylsulfonyl) phenyl ] -2-amino-1, 3-propanediol | |
| EP3752482A1 (en) | Process for preparation of bis-choline tetrathiomolybdate | |
| CN113173959B (en) | Method for removing impurities in system for enzymatically synthesizing sucrose-6-acetate | |
| CN113683607B (en) | Terilitine intermediate crystal form II and preparation method thereof | |
| CN117164464A (en) | Crystal form of trientine hydrate and preparation method thereof | |
| CN111875661B (en) | Method for separating and purifying abiraterone and dimer thereof | |
| CN116396312A (en) | Preparation method of isazomib citrate | |
| CN108069971B (en) | Refining method of pralatrexate intermediate | |
| CN110283210B (en) | Refining method of tenofovir disoproxil fumarate | |
| JP5419570B2 (en) | Method for purifying 2-acetylaminomethyl-4- (4-fluorobenzyl) morpholine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |