CN111925303A - Preparation method of ropivacaine hydrochloride impurity - Google Patents
Preparation method of ropivacaine hydrochloride impurity Download PDFInfo
- Publication number
- CN111925303A CN111925303A CN202010810084.0A CN202010810084A CN111925303A CN 111925303 A CN111925303 A CN 111925303A CN 202010810084 A CN202010810084 A CN 202010810084A CN 111925303 A CN111925303 A CN 111925303A
- Authority
- CN
- China
- Prior art keywords
- ropivacaine hydrochloride
- vilsmeier
- haack
- preparation
- reagent
- 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.)
- Pending
Links
- ZKMNUMMKYBVTFN-HNNXBMFYSA-N (S)-ropivacaine Chemical compound CCCN1CCCC[C@H]1C(=O)NC1=C(C)C=CC=C1C ZKMNUMMKYBVTFN-HNNXBMFYSA-N 0.000 title claims abstract description 52
- 229960001813 ropivacaine hydrochloride Drugs 0.000 title claims abstract description 52
- 239000012535 impurity Substances 0.000 title claims abstract description 46
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N Vilsmeier-Haack reagent Natural products CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 37
- UFFBMTHBGFGIHF-UHFFFAOYSA-N 2,6-dimethylaniline Chemical compound CC1=CC=CC(C)=C1N UFFBMTHBGFGIHF-UHFFFAOYSA-N 0.000 claims abstract description 28
- 238000006243 chemical reaction Methods 0.000 claims abstract description 26
- 238000002156 mixing Methods 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims description 26
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 21
- 239000003153 chemical reaction reagent Substances 0.000 claims description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- 238000005874 Vilsmeier-Haack formylation reaction Methods 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- 239000003960 organic solvent Substances 0.000 claims description 9
- 238000010791 quenching Methods 0.000 claims description 9
- 230000000171 quenching effect Effects 0.000 claims description 9
- 150000001266 acyl halides Chemical class 0.000 claims description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical group ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 150000004820 halides Chemical class 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- 238000001953 recrystallisation Methods 0.000 claims description 4
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 3
- 239000012346 acetyl chloride Substances 0.000 claims description 3
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 2
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 2
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 2
- 238000004440 column chromatography Methods 0.000 claims description 2
- 239000003208 petroleum Substances 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims 3
- 239000002994 raw material Substances 0.000 abstract description 5
- 238000007086 side reaction Methods 0.000 abstract description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000000843 powder Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000000605 extraction Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003589 local anesthetic agent Substances 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- LEBVLXFERQHONN-UHFFFAOYSA-N 1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide Chemical compound CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C LEBVLXFERQHONN-UHFFFAOYSA-N 0.000 description 1
- 229940052294 amide local anesthetics Drugs 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 229960003150 bupivacaine Drugs 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000002692 epidural anesthesia Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- NGAZZOYFWWSOGK-UHFFFAOYSA-N heptan-3-one Chemical compound CCCCC(=O)CC NGAZZOYFWWSOGK-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/12—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to hydrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a preparation method of ropivacaine hydrochloride impurities, which is obtained by mixing, reacting and purifying 2, 6-dimethylaniline and Vilsmeier-Haack reagent. The preparation method of the ropivacaine hydrochloride impurity has the advantages of low raw material cost and mild reaction conditions, the ropivacaine hydrochloride impurity can be generated by reacting only by mixing the reaction raw materials, the conditions such as temperature control and the like are not needed, the preparation method has low cost and no side reaction, and the ropivacaine hydrochloride impurity obtained by reaction has high purity and high yield.
Description
Technical Field
The invention relates to the field of medicine impurities, in particular to a preparation method of ropivacaine hydrochloride impurities.
Background
Ropivacaine hydrochloride is an amide local anesthetic, a long-acting amide local anesthetic developed by Astra, Sweden, and is mainly used for surgical anesthesia and epidural anesthesia. The ropivacaine hydrochloride has the dual effects of anesthesia and analgesia, and compared with amide local anesthetics such as bupivacaine, the ropivacaine hydrochloride has longer drug action time and lower toxicity to heart.
Impurities possibly generated in the production and storage processes of the ropivacaine hydrochloride not only affect the purity of the ropivacaine hydrochloride medicament, but also affect the curative effect of the medicament and possibly cause toxic and side effects. Therefore, the research on the impurities of the ropivacaine hydrochloride has important significance. A preparation method of ropivacaine hydrochloride impurity F with publication number CN105646482A discloses an impurity generated during the storage process of ropivacaine hydrochloride, which is mainly generated due to the degradation of ropivacaine hydrochloride. However, a method for preparing impurities in the synthesis process of ropivacaine hydrochloride has not been disclosed.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provide a preparation method of ropivacaine hydrochloride impurities.
In order to achieve the purpose, the invention adopts the technical scheme that: a preparation method of ropivacaine hydrochloride impurities is disclosed, wherein the chemical structural formula of the ropivacaine hydrochloride impurities is shown as a formula I;
the preparation method of the ropivacaine hydrochloride impurity comprises the steps of mixing 2, 6-dimethylaniline and a Vilsmeier-Haack reagent, reacting and purifying to obtain the ropivacaine hydrochloride impurity.
The synthesis route of the ropivacaine hydrochloride is shown in figure 1, impurities with a structure shown in a formula I can be generated in the synthesis process of the ropivacaine hydrochloride, and the inventor provides a preparation method of the ropivacaine hydrochloride impurities with the structure shown in the formula I through research.
Preferably, the method comprises the steps of:
(1) mixing and stirring 2, 6-dimethylaniline and a Vilsmeier-Haack reagent for reaction;
(2) adding water into the reaction system reacted in the step (1) for quenching, adjusting the pH value to be not less than 6, and extracting by using an organic solvent;
(3) concentrating and purifying to obtain the ropivacaine hydrochloride impurity.
The method is firstly quenched by water, can remove excessive Vilsmeier-Haack reagent and reduce the generation of side reaction, and is firstly quenched by water and then extracted by an organic solvent under the condition that the pH value is not less than 6, so that the extraction efficiency is high.
Preferably, in the step (2), the pH value is adjusted to be 6-14.
Preferably, in the step (2), the pH value is adjusted to 10-14.
The inventor discovers that the method has higher extraction efficiency by using the organic solvent for extraction under the condition that the pH value is 10-14, and the ropivacaine hydrochloride impurity prepared by the reaction has high purity and high yield.
Preferably, the Vilsmeier-Haack reagent comprises Vilsmeier-Haack acyl halide reagent and N, N-dimethylformamide, and the Vilsmeier-Haack acyl halide reagent is phosphorus oxychloride, phosphorus pentachloride, thionyl chloride, acetyl chloride or triphosgene.
The inventor discovers through research that when the Vilsmeier-Haack acyl halide reagent is phosphorus oxychloride, phosphorus pentachloride, thionyl chloride, acetyl chloride or triphosgene, the reaction efficiency is high, no side reaction occurs, and the impurity purity of the ropivacaine hydrochloride prepared is high.
Preferably, in the step (2), the ratio of the amounts of the substances of 2, 6-dimethylaniline, Vilsmeier-Haack acid halide reagent and N, N-dimethylformamide is 2, 6-dimethylaniline: Vilsmeier-Haack acid halide reagent: n, N-dimethylformamide (80-90): (80-90): (250-265).
According to the method, the ratio of the amount of the 2, 6-dimethylaniline, the Vilsmeier-Haack acyl halide reagent and the N, N-dimethylformamide is (80-90): (80-90): (250-265), the utilization rate of raw material reagents is high, and the preparation cost is favorably reduced.
Preferably, in the step (2), the organic solvent is dichloromethane, chloroform, ethyl acetate, toluene or petroleum ether.
The method adopts the organic solvent for extraction, the extraction rate is high, and the impurity yield of the prepared ropivacaine hydrochloride is high.
Preferably, the concentration and purification method comprises column chromatography and recrystallization, and the solvent used for recrystallization is methanol, ethanol, n-propanol, isopropanol, propyl butanone, methyl isobutyl ketone, diethyl ether, isopropyl ether or ethyl acetate.
The invention has the beneficial effects that: the invention provides a preparation method of ropivacaine hydrochloride impurities, which has the advantages of low raw material cost, mild reaction conditions, low preparation method cost, no side reaction, high purity and high yield of the ropivacaine hydrochloride impurities prepared by reaction, wherein the ropivacaine hydrochloride impurities can be generated by reacting only by mixing reaction raw materials without controlling the conditions such as temperature and the like.
Drawings
Figure 1 is a scheme showing the synthesis of ropivacaine hydrochloride.
FIG. 2 is a synthesis scheme of the preparation of ropivacaine hydrochloride impurity according to the example of the present invention.
Detailed Description
To better illustrate the objects, aspects and advantages of the present invention, the present invention will be further described with reference to specific examples.
The invention provides a preparation method of ropivacaine hydrochloride impurities, wherein the chemical structural formula of the ropivacaine hydrochloride impurities is shown as a formula I;
the preparation method of the ropivacaine hydrochloride impurity comprises the steps of mixing 2, 6-dimethylaniline, a Vilsmeier-Haack acyl halide reagent and N, N-dimethylformamide, reacting and purifying to obtain the ropivacaine hydrochloride impurity.
Further, the method comprises the steps of:
(1) mixing and stirring 2, 6-dimethylaniline, a Vilsmeier-Haack acyl halide reagent and N, N-dimethylformamide for reaction;
(2) adding water into the reaction system reacted in the step (1) for quenching, adjusting the pH value to be not less than 6, and extracting by using an organic solvent;
(3) concentrating and purifying to obtain the ropivacaine hydrochloride impurity.
Example 1
The preparation method of the ropivacaine hydrochloride impurity provided by the embodiment of the invention comprises the following steps:
(1) 5.2g of 2, 6-dimethylaniline (0.043mol), 13.0g of phosphorus oxychloride (0.085mol) and 40mLN, N-dimethylformamide are mixed and stirred for reaction until the reaction is finished, and the reaction is judged to be finished by a dot plate method;
(2) adding water into the reaction system reacted in the step (1) for quenching, adjusting the pH value to 12 by using sodium hydroxide, and extracting by using toluene;
(3) the organic phases were combined, spin dried, column filtered and concentrated to dryness to give a white solid powder.
According to determination, 4.0g of white solid powder prepared in the embodiment is obtained, the purity is 99.0%, and the result is shown by mass spectrum and nuclear magnetic detection1H-NMR(CDCl3，400MHz)：2.17(6H,s)，2.99(6H,s)，6.60～7.34(4H,m)；m/z：177.15[M+H]Ropivacaine hydrochloride impurity of formula I.
Example 2
The preparation method of the ropivacaine hydrochloride impurity provided by the embodiment of the invention comprises the following steps:
(1) 5.2g of 2, 6-dimethylaniline (0.043mol), 13.0g of thionyl chloride (0.085mol) and 40mLN, N-dimethylformamide are mixed and stirred for reaction until the reaction is finished, and the reaction is judged to be finished by a dot plate method;
(2) adding water into the reaction system reacted in the step (1) for quenching, adjusting the pH value to 10 by using sodium hydroxide, and extracting by using dichloromethane;
(3) and (3) combining the organic phases, spin-drying, adding 20ml of acetone, heating to complete dissolution, cooling to 10-20 ℃, crystallizing, filtering and drying to obtain light yellow solid powder.
According to determination, 3.6g of light yellow solid powder prepared in the embodiment is obtained, the purity is 96.5%, and the result is obtained through mass spectrum and nuclear magnetic detection1H-NMR(CDCl3，400MHz)：2.17(6H,s)，2.99(6H,s)，6.60～7.34(4H,m)；m/z：177.15[M+H]Ropivacaine hydrochloride impurity of formula I.
Example 3
As a method for preparing ropivacaine hydrochloride impurities in the embodiment of the present invention, the only difference between the embodiment and the embodiment 1 is: (2) adding water into the reaction system reacted in the step (1) for quenching, adjusting the pH value to 14 by using sodium hydroxide, and extracting by using toluene to obtain white solid powder with the purity of 98.6 percent and 4.2 g.
Example 4
As a method for preparing ropivacaine hydrochloride impurities in the embodiment of the present invention, the only difference between the embodiment and the embodiment 1 is: (2) adding water into the reaction system reacted in the step (1) for quenching, adjusting the pH value to 10 by using sodium hydroxide, and extracting by using toluene to obtain 3.6g of white solid powder with the purity of 98.8%.
Example 5
As a method for preparing ropivacaine hydrochloride impurities in the embodiment of the present invention, the only difference between the embodiment and the embodiment 1 is: (2) adding water into the reaction system reacted in the step (1) for quenching, adjusting the pH value to 8 by using sodium hydroxide, and extracting by using toluene to obtain 3.1g of white solid powder with the purity of 99.1%.
Example 6
As a method for preparing ropivacaine hydrochloride impurities in the embodiment of the present invention, the only difference between the embodiment and the embodiment 1 is: (2) adding water into the reaction system reacted in the step (1) for quenching, adjusting the pH value to 6 by using sodium hydroxide, and extracting by using toluene to obtain 2.0g of white solid powder with the purity of 99.1%.
From the results of the embodiment 1 and the embodiments 3 to 6, it is known that the method has higher extraction efficiency and higher yield by using the organic solvent for extraction under the condition that the pH value is 10-14, and is beneficial to reducing the cost.
Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention and not for limiting the protection scope of the present invention, and although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.
Claims (8)
1. A preparation method of ropivacaine hydrochloride impurities is characterized in that the chemical structural formula of the ropivacaine hydrochloride impurities is shown as a formula I;
the preparation method of the ropivacaine hydrochloride impurity comprises the steps of mixing 2, 6-dimethylaniline and a Vilsmeier-Haack reagent, reacting and purifying to obtain the ropivacaine hydrochloride impurity.
2. The method for preparing according to claim 1, characterized in that it comprises the following steps:
(1) mixing and stirring 2, 6-dimethylaniline and a Vilsmeier-Haack reagent for reaction;
(2) adding water into the reaction system reacted in the step (1) for quenching, adjusting the pH value to be not less than 6, and extracting by using an organic solvent;
(3) concentrating and purifying to obtain the ropivacaine hydrochloride impurity.
3. The method according to claim 2, wherein in the step (2), the pH is adjusted to 6 to 14.
4. The method according to claim 3, wherein in the step (2), the pH is adjusted to 10 to 14.
5. The method of claim 2, wherein the Vilsmeier Haack reagent comprises Vilsmeier Haack acyl halide reagent and N, N-dimethylformamide, and the Vilsmeier Haack acyl halide reagent is phosphorus oxychloride, phosphorus pentachloride, thionyl chloride, acetyl chloride or triphosgene.
6. The method according to claim 5, wherein in the step (2), the ratio of the amounts of the substances of 2, 6-dimethylaniline, Vilsmeier-Haack acid halide reagent and N, N-dimethylformamide is 2, 6-dimethylaniline: Vilsmeier-Haack acid halide reagent: n, N-dimethylformamide (80-90): (80-90): (250-265).
7. The method according to claim 2, wherein in the step (2), the organic solvent is dichloromethane, chloroform, ethyl acetate, toluene, or petroleum ether.
8. The preparation method according to claim 2, wherein the concentration and purification method comprises column chromatography and recrystallization, and the solvent used for recrystallization is methanol, ethanol, n-propanol, isopropanol, methyl ethyl ketone, methyl isobutyl ketone, diethyl ether, isopropyl ether or ethyl acetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010810084.0A CN111925303A (en) | 2020-08-12 | 2020-08-12 | Preparation method of ropivacaine hydrochloride impurity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010810084.0A CN111925303A (en) | 2020-08-12 | 2020-08-12 | Preparation method of ropivacaine hydrochloride impurity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111925303A true CN111925303A (en) | 2020-11-13 |
Family
ID=73310906
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010810084.0A Pending CN111925303A (en) | 2020-08-12 | 2020-08-12 | Preparation method of ropivacaine hydrochloride impurity |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111925303A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3929883A (en) * | 1972-03-29 | 1975-12-30 | Ciba Geigy Corp | Phenylformamidine derivatives |
-
2020
- 2020-08-12 CN CN202010810084.0A patent/CN111925303A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3929883A (en) * | 1972-03-29 | 1975-12-30 | Ciba Geigy Corp | Phenylformamidine derivatives |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102863487B (en) | Process for preparing 20,23-bi-piperidyl-5-O-carbon mould amine glycosyl-tylosin lactone | |
| CN113121416A (en) | Preparation method of lefenacin | |
| CN113416150B (en) | Synthetic method of lobaplatin intermediate | |
| CN111925317B (en) | Ropivacaine hydrochloride impurity and preparation method thereof | |
| CN111072552B (en) | Preparation method of cilnidipine | |
| CN111925303A (en) | Preparation method of ropivacaine hydrochloride impurity | |
| CN114057642B (en) | Synthetic method of mickey ammonium chloride intermediate | |
| CN116178162A (en) | Green and rapid preparation method of nitrate radical transfer reagent | |
| CN111269128B (en) | Synthesis method of 1,1' - (hexa-2, 4-diyne-1, 6-diyl) bis (3-alkyl urea) compound | |
| CN112110879B (en) | Preparation method of sulcardine free alkali | |
| CN109574866B (en) | Preparation method of 2, 6-dimethylaniline long-chain compound | |
| CN114805049A (en) | Preparation method of 10-oxo-nonadecane diacid | |
| CN111100042B (en) | Preparation method of 2-methoxy-5-sulfonamide benzoic acid | |
| CN113999120A (en) | Preparation method of halogenated aniline compound | |
| CN108409561B (en) | Preparation method of 5-aminolevulinic acid hydrochloride and intermediate | |
| CN112479970A (en) | Indole beta-site alkylation method without participation of transition metal | |
| CN111747926A (en) | Improved method for synthesis process of free hydroxypiperone alkali | |
| CN107629039B (en) | The preparation method and intermediate of deuterated acrylamide | |
| CN107573279B (en) | Synthesis method of amlodipine besylate degradation impurities | |
| CN113024472A (en) | Preparation method of lung cancer targeted drug dacomitinib | |
| CN107286040B (en) | Method for synthesizing colchicine | |
| CN116514622B (en) | Method for simply synthesizing alpha-bromomethyl ketone compound | |
| CN115073313B (en) | Method for synthesizing terbutaline sulfate impurity C | |
| CN118255679A (en) | Synthesis method of 1-amino-2, 2-dimethylcyclopropane carboxylic acid | |
| CN116217632A (en) | Preparation method of deuterated cytidine derivative |
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 | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20201113 |