CN110343036A - A kind of preparation method of cyclopentyl phenyl acetaldehyde - Google Patents
A kind of preparation method of cyclopentyl phenyl acetaldehyde Download PDFInfo
- Publication number
- CN110343036A CN110343036A CN201910628313.4A CN201910628313A CN110343036A CN 110343036 A CN110343036 A CN 110343036A CN 201910628313 A CN201910628313 A CN 201910628313A CN 110343036 A CN110343036 A CN 110343036A
- Authority
- CN
- China
- Prior art keywords
- preparation
- cyclopentyl phenyl
- added
- grease
- phenyl acetaldehyde
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
- C07C45/57—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom
- C07C45/58—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom in three-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
Abstract
The invention discloses a kind of preparation methods of cyclopentyl phenyl acetaldehyde, including, using cyclopentyl phenyl ethylene oxide as raw material, using lewis acid as catalyst, it reacts and cyclopentyl phenyl acetaldehyde is made, it specifically includes: cyclopentyl phenyl ethylene oxide is dissolved in organic solvent, lewis acid is added as catalyst, it is stirred to react, adds water quenching reaction, extractant extraction is then added, take organic phase, desiccant is then added, is concentrated to get grease after filtering, obtained grease is obtained into cyclopentyl phenyl acetaldehyde through column chromatography for separation.Preparation method provided by the present invention can provide the reference substance of Qualitative and quantitative analysis for the detection of amyl ethyl quin ether hydrochloride, and the quality standard of amyl ethyl quin ether hydrochloride can be improved；Prepare that impurity cyclopentyl phenyl acetaldehyde is easy to operate, and the raw material used is easy to get, the impurity preparation cost is low, with high purity and quality controllable.
Description
Technical field
The present invention relates to pharmaceutical technology fields, and in particular to a kind of preparation method of cyclopentyl phenyl acetaldehyde.
Background technique
Amyl ethyl quin ether hydrochloride is a kind of potent anticholinergic agent of China's independent development, the entitled 3- (2- cyclopenta -2- of chemistry
Hydroxyl -2- phenyl ethoxy) quinuclidine hydrochloride, acute treatment and poisoning later period for organophosphorus poison (pesticide) poisoning
Or after cholinesterase (ChE) aging maintain atropinization (atropinization refer to organophosphorus poisoning patient through application doses Ah
Make body boundary in the atropine maximum physiological tolerance limit and atropinism critical state between the two after tropine).It is changed
It is as follows to learn structural formula:
The chemical structure of amyl ethyl quin ether hydrochloride is tertiary ammonium salt, and intracerebral, blockage of acetylcholine pair can be entered by blood-brain barrier
The agonism of intracerebral poison Zhang alkali receptor (m receptor) and nicotine receptor (n receptor), therefore can the organic phosphorus poison of preferable antagonism
Maincenter poisoning symptom caused by (pesticide) is poisoned, such as convulsions, maincenter respiratory and circulatory failure and dysphoria；Meanwhile in periphery
Also there is stronger blockage of acetylcholine to the agonism of m receptor, it equally can preferable antagonism organophosphorus poison (pesticide) poisoning
Caused poison alkali sample poisoning symptom, as bronchial muscular spasm and secretion increases, perspire, salivate, miosis and gastrointestinal tract are flat
Sliding muscle spasmus or contraction etc., moreover it is possible to increase respiratory rate and respiratory flow, due to its to M2 receptor without obvious effect, therefore to heart rate
It has no significant effect；To periphery n receptor without obvious antagonism.It is also indicated that by every preclinical study, with stronger peace
Quan Xing, being mainly manifested in there is no potential toxicity each system of whole body and target organ, have that tolerance is good, pharmacological action is strong
The features such as.
Therefore, amyl ethyl quin ether hydrochloride preanesthetic medication, organic phosphorus pesticide poisoning rescue, shock, respiratory disease,
Start to promote in the clinical fields such as cardiovascular disease, alternative most common similar medicine atropine and hyoscine both at home and abroad are used for
Clinical cholinolytic treatment.
In conjunction with the analysis of Production Technology of amyl ethyl quin ether hydrochloride, it is likely that have the generation of cyclopentyl phenyl acetaldehyde impurities, will affect
The quality of amyl ethyl quin ether hydrochloride.The approach that cyclopentyl phenyl acetaldehyde impurities generate specifically includes that (1) production amyl ethyl quin ether hydrochloride makes
Open loop side reaction occurs for intermediate cyclopentyl phenyl ethylene oxide, to generate a small amount of cyclopentyl phenyl acetaldehyde impurities；
(2) amyl ethyl quin ether hydrochloride is likely occurred ether bond rupture during production and storage, and degradation generates a small amount of cyclopentyl phenyl
Acetaldehyde impurities.
As the requirement that impurity in drug research and development is studied in China is increasingly stringent, especially to the side reaction product of drug and
The researchs such as catabolite are paid special attention to, and are carried out the rigorous further investigation of specification, are controlled the limit model in safe and reasonable
In enclosing.Therefore impurity research is extremely important in drug development process, while the foundation of quality standard needs a certain amount of standard items.
To sum up, the impurity cyclopentyl phenyl acetaldehyde of amyl ethyl quin ether hydrochloride is prepared with important meaning, and preparing the impurity can be used for hydrochloric acid
The Qualitative and quantitative analysis of amyl ethyl quin ether impurity is studied, and the quality of amyl ethyl quin ether hydrochloride is helped to improve.
Summary of the invention
The present invention compensates for the shortcomings of the prior art, provides a kind of preparation method of cyclopentyl phenyl acetaldehyde.
The present invention adopts the following technical scheme:
A kind of preparation method of cyclopentyl phenyl acetaldehyde, including, using cyclopentyl phenyl ethylene oxide as raw material, with Louis
Acid is used as catalyst, reacts and cyclopentyl phenyl acetaldehyde is made.
In the above-mentioned technical solutions, the preparation method specifically includes the following steps:
S1, cyclopentyl phenyl ethylene oxide is dissolved in organic solvent, lewis acid is added as catalyst, stirring is anti-
It answers；
S2 plus water quenching reaction are then added extractant extraction, take organic phase, desiccant is then added, is concentrated after filtering
Obtain grease；
S3, grease obtained in step S2 is obtained into cyclopentyl phenyl acetaldehyde through column chromatography for separation.
Further, in the above-mentioned technical solutions, the lewis acid be alchlor, indium trichloride, tin tetrachloride and
One of zinc dichloride, preferably indium trichloride.
Ethylene oxide and its derivative are ternary cyclic ethers, and three-membered ring has compared with hightension, under acid or alkaline conditions
Ring-opening reaction easily occurs.Use general acid or alkali as the catalyst of ring-opening reaction, carries out the asymmetric epoxy second of structure
When alkane derivatives ring-opening reaction, poor selectivity has multiple open-loop products, and yield is unstable；And select lewis acid conduct
Catalyst has selectivity strong, reacts mild advantage, the easily separated purifying of obtained product.
Still further, in the above-mentioned technical solutions, the additional amount of the lewis acid and cyclopentyl phenyl ethylene oxide
Molar ratio is 0.1-1:1, preferably 0.6-0.8:1.
Further, in the above-mentioned technical solutions, the temperature of the reaction is 10-50 DEG C, preferably 20-30 DEG C.
Further, in the above-mentioned technical solutions, the time of the reaction is 1-5h, preferably 3-4h.
Use lewis acid as catalyst, selects preferred reaction temperature and reaction time, ring-opening reaction high conversion rate
And good, the easily separated purifying of selectivity, obtain the product of purity is high.
In the above-mentioned technical solutions, in step S1, the organic solvent is tetrahydrofuran.
In the above-mentioned technical solutions, in step S2, the extractant is in ethyl acetate, methylene chloride and chloroform
One kind, preferably ethyl acetate.
In the above-mentioned technical solutions, in step S2, the desiccant is anhydrous sodium sulfate.
In the above-mentioned technical solutions, in step S3, the column chromatography procedure is specifically included:
A1, grease is dissolved in ethyl acetate, adds silica gel mixed sample, be concentrated to dryness, it is spare to have been mixed sample silica gel, the silicon
The addition quality of glue is 1-3 times of grease；
A2, silica gel is weighed, addition hexane pours into glass column after mixing evenly to be settled, and having mixed in step a1 is then added
Sample silica gel, the addition quality of the silica gel are 10-50 times, preferably 20-25 times of grease；
A3, the mixed solution elution that hexane and ethyl acetate is added, collect product point, are concentrated to dryness to obtain the final product, the hexane
Additional amount volume ratio with ethyl acetate is 1-15:1, preferably 3-8:1.
Compared with prior art, the present invention has the advantage that
Preparation method provided by the present invention can provide the control of Qualitative and quantitative analysis for the detection of amyl ethyl quin ether hydrochloride
The quality standard of amyl ethyl quin ether hydrochloride can be improved in product；Prepare that impurity cyclopentyl phenyl acetaldehyde is easy to operate, and the raw material used is easy
, the impurity preparation cost is lower, with high purity and quality controllable.
Detailed description of the invention
Fig. 1 is the nuclear magnetic resonance spectroscopy (H-NMR) of the cyclopentyl phenyl acetaldehyde prepared in the embodiment of the present invention 1；
Fig. 2 is the mass spectrum (MS) of the cyclopentyl phenyl acetaldehyde prepared in the embodiment of the present invention 1；
Fig. 3 is the HPLC-UV detection (HPLC) of the cyclopentyl phenyl acetaldehyde prepared in the embodiment of the present invention 1.
Specific embodiment
With reference to the accompanying drawings and examples, specific embodiments of the present invention will be described in further detail.
Following embodiment is merely to illustrate the present invention, the protection scope being not intended to limit the invention.
Experimental method used in following embodiment is conventional method unless otherwise specified.
Material used in following embodiment, reagent etc., are commercially available unless otherwise specified.
Embodiment 1
A kind of preparation method of cyclopentyl phenyl acetaldehyde, comprising the following steps:
(1) cyclopentyl phenyl ethylene oxide 20g is weighed, is added in reaction flask, tetrahydrofuran 200g, stirring and dissolving is added
Afterwards, indium trichloride 16.7g is added；
(2) stir, 25-30 DEG C is reacted 3 hours, after reaction plus 200g water quenching reaction, then plus ethyl acetate extraction, every time
100g merges organic addition anhydrous sodium sulfate 50g drying 1 hour, after dry, be filtered to remove sodium sulphate, be concentrated to give grease
12.4g。
(3) gained grease add ethyl acetate 20g dissolve, then plus silica gel 25g stir evenly, be concentrated to dryness, it is spare.It weighs
Silica gel 300g, adds hexane to stir evenly, and pours into glass column and settles, and after filling column, is added with sample silica gel, adds hexane
It is eluted with the mixed solution of ethyl acetate, the volume ratio of hexane and ethyl acetate is 5:1.Product point is collected, is concentrated to dryness, obtains miscellaneous
Matter cyclopentyl phenyl acetaldehyde 2.65g.
It takes sample appropriate, after being dissolved with DMSO-d6, carries out nuclear magnetic resonance spectroscopy (H-NMR) analysis.
Fig. 1 is the nuclear magnetic resonance spectroscopy of cyclopentyl phenyl acetaldehyde prepared by the embodiment of the present invention, and the result of analysis chart 1 can
Know, corresponding 1 hydrogen of δ 9.66-9.67ppm is attributed to aldehyde radical hydrogen；δ 7.28-7.37ppm corresponds to 5 hydrogen, is attributed to phenyl ring hydrogen；δ
3.39-3.42ppm corresponds to 1 hydrogen, is attributed to the methine hydrogen adjacent with aldehyde radical；δ 2.50-2.51ppm corresponds to 1 hydrogen, ownership
For the methine hydrogen of cyclopenta；δ 1.00-1.52ppm corresponds to 8 hydrogen, is attributed to four methylene hydrogen of cyclopenta.
Take sample appropriate, using ESI negative ion mode, direct injected carries out mass spectrum (MS) analysis.
Fig. 2 is the mass spectrum of cyclopentyl phenyl acetaldehyde prepared by the embodiment of the present invention, the result of analysis chart 2 it is found that bear from
Detected value is 187.1 under sub- detection mode, is cyclopentyl phenyl acetaldehyde anion (C13H15O)-[M] of molecular weight-Ion.
Efficient liquid phase test method: precision weighs this product, is dissolved with acetonitrile and quantifies dilution and is made in every 1ml containing about 1mg
Solution, as test solution；It is filler with octadecylsilane chemically bonded silica, using 40% acetonitrile as mobile phase, flow velocity
For 1.0ml/min；Detection wavelength is 205nm, 30 DEG C of column temperature.It takes 20 μ l of test solution to inject liquid chromatograph, records chromatography
Figure.The retention time of cyclopentyl phenyl acetaldehyde is about 16min under the chromatographic condition.
Fig. 3 is the HPLC-UV detection of cyclopentyl phenyl acetaldehyde prepared by the embodiment of the present invention.
From the result in Fig. 3, it can be concluded that, cyclopentyl phenyl acetaldehyde appearance time is 16.318min, and purity is
99.05%.
Embodiment 2
A kind of preparation method of cyclopentyl phenyl acetaldehyde, comprising the following steps:
(1) cyclopentyl phenyl ethylene oxide 25g is weighed, is added in reaction flask, tetrahydrofuran 300g, stirring and dissolving is added
Afterwards, indium trichloride 18.5g is added.
(2) stir, 20~25 DEG C are reacted 4 hours, after reaction plus 250g water quenching reaction, then plus ethyl acetate extraction, often
Secondary 125g merges organic addition anhydrous sodium sulfate 50g drying 2 hours, after dry, be filtered to remove sodium sulphate, be concentrated to give grease
16.3g。
(3) gained grease add ethyl acetate 30g dissolve, then plus silica gel 32g stir evenly, be concentrated to dryness, it is spare.It weighs
Silica gel 350g, adds hexane to stir evenly, and pours into glass column and settles, and after filling column, is added with sample silica gel, adds hexane
It is eluted with the mixed solution of ethyl acetate, the volume ratio of hexane and ethyl acetate is 4:1.Product point is collected, is concentrated to dryness, obtains miscellaneous
Matter cyclopentyl phenyl acetaldehyde 3.03g.
Embodiment 3
A kind of preparation method of cyclopentyl phenyl acetaldehyde, comprising the following steps:
(1) cyclopentyl phenyl ethylene oxide 10g is weighed, is added in reaction flask, tetrahydrofuran 100g, stirring and dissolving is added
Afterwards, indium trichloride 7.1g is added.
(2) stir, 25~30 DEG C are reacted 4 hours, after reaction plus 100g water quenching reaction, then plus ethyl acetate extraction, often
Secondary 50g merges organic addition anhydrous sodium sulfate 30g drying 1 hour, after dry, be filtered to remove sodium sulphate, be concentrated to give grease
5.9g。
(3) gained grease add ethyl acetate 10g dissolve, then plus silica gel 12g stir evenly, be concentrated to dryness, it is spare.It weighs
Silica gel 120g, adds hexane to stir evenly, and pours into glass column and settles, and after filling column, is added with sample silica gel, adds hexane
It is eluted with the mixed solution of ethyl acetate, the volume ratio of hexane and ethyl acetate is 6:1.Product point is collected, is concentrated to dryness, obtains miscellaneous
Matter cyclopentyl phenyl acetaldehyde 1.14g.
Finally, being not intended to limit the scope of the present invention the above is only preferred embodiment of the invention.It is all this
Within the spirit and principle of invention, any modification, equivalent replacement, improvement and so on should be included in protection model of the invention
Within enclosing.
Claims (9)
1. a kind of preparation method of cyclopentyl phenyl acetaldehyde, which is characterized in that including being original with cyclopentyl phenyl ethylene oxide
Material is reacted and cyclopentyl phenyl acetaldehyde is made using lewis acid as catalyst.
2. preparation method according to claim 1, which is characterized in that specifically includes the following steps:
S1, cyclopentyl phenyl ethylene oxide is dissolved in organic solvent, lewis acid is added as catalyst, is stirred to react；
S2 plus water quenching reaction are then added extractant extraction, take organic phase, desiccant is then added, is concentrated to get after filtering
Grease；
S3, grease obtained in step S2 is obtained into cyclopentyl phenyl acetaldehyde through column chromatography for separation.
3. preparation method according to claim 1 or 2, which is characterized in that the lewis acid is alchlor, tri-chlorination
One of indium, tin tetrachloride and zinc dichloride, preferably indium trichloride.
4. preparation method according to claim 1-3, which is characterized in that the lewis acid and cyclopentyl phenyl
The additional amount molar ratio of ethylene oxide is 0.1-1:1, preferably 0.6-0.8:1.
5. preparation method according to claim 1 or 2, which is characterized in that
The temperature of the reaction is 10-50 DEG C, preferably 20-30 DEG C；
And/or the time of the reaction is 1-5h, preferably 3-4h.
6. preparation method according to claim 2, which is characterized in that in step S1, the organic solvent is tetrahydrofuran.
7. preparation method according to claim 2, which is characterized in that in step S2, the extractant is ethyl acetate, two
One of chloromethanes and chloroform, preferably ethyl acetate.
8. preparation method according to claim 2, which is characterized in that in step S2, the desiccant is anhydrous sodium sulfate.
9. preparation method according to claim 2, which is characterized in that in step S3, the column chromatography procedure is specifically included:
A1, grease is dissolved in ethyl acetate, adds silica gel mixed sample, be concentrated to dryness, mixed that sample silica gel is spare, the silica gel
1-3 times that quality is grease is added；
A2, silica gel is weighed, addition hexane pours into glass column after mixing evenly to be settled, and is then added in step a1 and has been mixed sample silicon
Glue, the addition quality of the silica gel are 10-50 times, preferably 20-25 times of grease；
A3, the mixed solution elution that hexane and ethyl acetate is added, collect product point, are concentrated to dryness to obtain the final product, the hexane and second
The additional amount volume ratio of acetoacetic ester is 1-15:1, preferably 3-8:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910628313.4A CN110343036A (en) | 2019-07-12 | 2019-07-12 | A kind of preparation method of cyclopentyl phenyl acetaldehyde |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910628313.4A CN110343036A (en) | 2019-07-12 | 2019-07-12 | A kind of preparation method of cyclopentyl phenyl acetaldehyde |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110343036A true CN110343036A (en) | 2019-10-18 |
Family
ID=68175067
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910628313.4A Pending CN110343036A (en) | 2019-07-12 | 2019-07-12 | A kind of preparation method of cyclopentyl phenyl acetaldehyde |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110343036A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111925281A (en) * | 2020-09-04 | 2020-11-13 | 江苏恩华药业股份有限公司 | Preparation method of penehyclidine hydrochloride impurity 2-cyclopentyl-2-phenylacetaldehyde |
-
2019
- 2019-07-12 CN CN201910628313.4A patent/CN110343036A/en active Pending
Non-Patent Citations (4)
| Title |
|---|
| ALBERT CABRÉ等: "MildIridium-Catalysed Isomerization of Epoxides.ComputationalInsights and Applicationto the Synthesisof β-AlkylAmines", 《ADV. SYNTH. CATAL.》 * |
| BRINDABAN C. RANU等: "Indium(III) Chloride-Promoted Rearrangement of Epoxides: A Selective Synthesis of Substituted Benzylic Aldehydes and Ketones", 《J. ORG. CHEM.》 * |
| HUMBERT, NICOLAS等: "An air-stable cationic iridium hydride as a highly active and general catalyst for the isomerization of terminal epoxides", 《CHEMICAL COMMUNICATIONS》 * |
| JIAN-HUA XIE等: "Ru-Catalyzed Asymmetric Hydrogenation of Racemic Aldehydes via Dynamic Kinetic Resolution: Efficient Synthesis of Optically Active Primary Alcohols", 《J. AM. CHEM. SOC.》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111925281A (en) * | 2020-09-04 | 2020-11-13 | 江苏恩华药业股份有限公司 | Preparation method of penehyclidine hydrochloride impurity 2-cyclopentyl-2-phenylacetaldehyde |
| CN111925281B (en) * | 2020-09-04 | 2022-04-15 | 江苏恩华药业股份有限公司 | Preparation method of penehyclidine hydrochloride impurity 2-cyclopentyl-2-phenylacetaldehyde |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Meltzer et al. | Substituted 3-phenyltropane analogs of cocaine: synthesis, inhibition of binding at cocaine recognition sites, and positron emission tomography imaging | |
| Jefford et al. | Synthesis, structure, and antimalarial activity of some enantiomerically pure, cis‐fused cyclopenteno‐1, 2, 4‐trioxanes | |
| CN105440049B (en) | A kind of method for preparing high-purity milbemycin oxime | |
| CN106349238A (en) | Preparation method of ipratropium bromide | |
| CN111410658B (en) | Impurity A and impurity B of midazolam or pharmaceutical composition thereof and application thereof | |
| CN110343036A (en) | A kind of preparation method of cyclopentyl phenyl acetaldehyde | |
| CN108047046B (en) | Emodin succinyl ester compound and preparation method and application thereof | |
| CN106518862B (en) | The preparation method of impurity in a kind of amyl ethyl quin ether hydrochloride | |
| CN105439925A (en) | Preparation method for lipoic acid polymer impurities and detection method for lipoic acid polymer impurities | |
| CN114479108A (en) | Layered super-hydrophilic Ti-Cu-MOFs and preparation method and application thereof | |
| CN106938998B (en) | Synthetic method of the canagliflozin in relation to substance | |
| McPherson et al. | Resolution and in Vitro and Initial in Vivo Evaluation of Isomers of Iodine-125-Labeled 1-Azabicyclo [2.2. 2] oct-3-yl. alpha.-Hydroxy-. alpha.-(1-iodo-1-propen-3-yl)-. alpha.-phenylacetate: A High-Affinity Ligand for the Muscarinic Receptor | |
| CN114702494B (en) | Automatic continuous flow semisynthesis method of vincamine | |
| CN112028887B (en) | Penehyclidine hydrochloride impurity and preparation method thereof | |
| CN115260272A (en) | Cholesterol selenocyanate compound and preparation method thereof | |
| US20230026724A1 (en) | Substituted nitrogen heterocyclic compound and anesthetic effect thereof | |
| DE102011052348B3 (en) | Precursor compounds for the radiosynthesis of [18F] norchlor-fluoro-homoepibatidine | |
| CN103804366B (en) | Lafutidine crystal compound | |
| CN108929269B (en) | Benzisoquinoline non-depolarizing muscle relaxant and preparation method and application thereof | |
| CN104072345B (en) | A kind of method being applicable to prepare 1-cyclopentyl-2-methoxyl group-1-phenylethyl alcohol | |
| CN104447649B (en) | Methyl naphtho-[1,2-b] amide compounds and pharmaceutically acceptable salt and its preparation method and application thereof | |
| CN108912018A (en) | The preparation method and its usage of impurity compound in a kind of key intermediate for synthesizing Sulpiride | |
| CN112457362B (en) | Halogenated tetracyclic triterpene derivative and preparation and application thereof | |
| CN109180478B (en) | Diphenheptane compounds, preparation method and application thereof | |
| US20230089353A1 (en) | Method for the preparation of n-monofluoroalkyl tropanes and their use |
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: 20191018 |