CN113582818B - Synthesis method of 3-halogen-2-alkylphenol - Google Patents
Synthesis method of 3-halogen-2-alkylphenol Download PDFInfo
- Publication number
- CN113582818B CN113582818B CN202111006568.0A CN202111006568A CN113582818B CN 113582818 B CN113582818 B CN 113582818B CN 202111006568 A CN202111006568 A CN 202111006568A CN 113582818 B CN113582818 B CN 113582818B
- Authority
- CN
- China
- Prior art keywords
- hours
- organic phase
- reduced pressure
- under
- methylphenol
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/16—Preparation of ethers by reaction of esters of mineral or organic acids with hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthesis method of 3-halogen-2-alkylphenol, belonging to the technical field of organic synthesis. 2, 6-dihaloalkylbenzene is used as a raw material, nucleophilic substitution is carried out on the raw material and dibenzyl alcohol in the presence of inorganic alkali, then Pd/C hydrogenation debenzylation reaction is carried out, or Grignard exchange is carried out on the raw material and metallic magnesium in the presence of n-butyl bromide/chlorine, and then air/oxygen is introduced to obtain the 3-halogen-2-alkylphenol. The method has the advantages of high regioselectivity, good yield, simple operation flow and the like, and the purity of the obtained product can reach more than 99.5 percent.
Description
Technical Field
The invention relates to a synthesis method of 3-halogen-2-alkylphenol, belonging to the field of organic synthesis.
Background
The 3-halogen-2-alkylphenol is an important intermediate of medicines, pesticides, dyes and the like, and the aromatic ring functional group of the 3-halogen-2-alkylphenol can be used for deriving aldehydes, carboxylic acids, cyano groups and the like from the alkyl, various substitution reactions from halogen, chemical reactions from phenolic hydroxyl groups to form ethers and the like, so that the 3-halogen-2-alkylphenol has wide application. Document [ Journal of Medicinal Chemistry,2017,60,1417-1431] reports 3-bromo-2-methylphenol as a main raw material for the synthesis of GPR40 agonists for the treatment of diabetes. The chemical formula of the medicine is as follows:
patent WO2017/90002,2017, a2 reports that 3-fluoro-2-methylphenol is useful for the synthesis of a pharmaceutical composition for the prevention or treatment of diseases or disorders associated with abnormal PI3K activity, such as inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, immunooncology, renal cancer, hepatitis c, hematological malignancies and multiple myeloma. The chemical formula of the medicine is as follows:
the existing synthesis method of the compound mainly adopts 2-methyl-3-haloaniline as a raw material, and 2-methyl-3-halophenol is obtained through diazotization and hydrolysis. The reaction equation is as follows:
patent WO2015/124651,2015,a1 reports that 1 equivalent of 1, 3-dichloro-2-methylbenzene is reacted with 3.0 equivalent of aqueous KOH (85%) in the presence of 10.0 equivalents of methanol to give 3-chloro-2-methylphenol in an isolated yield of 86% after 20 hours at up to 200 ℃; the reaction equation is as follows:
in the method, potassium chloride is generated after the reaction, so that the corrosion is easy to occur to the reaction kettle in an alkaline high-temperature environment, and the service life of the reaction kettle is reduced.
Therefore, the development of a synthetic method which is more suitable for industrial production has important research significance.
Disclosure of Invention
In order to overcome the technical defects, the invention discloses a synthesis method of 3-halogen-2-alkylphenol.
2, 6-dihaloalkylbenzene is used as a raw material, nucleophilic substitution is carried out on the raw material and dibenzyl alcohol in the presence of inorganic alkali, then Pd/C hydrogenation debenzylation reaction is carried out, or Grignard exchange is carried out on the raw material and n-butyl bromide/chlorine and magnesium, and then air/oxygen is introduced to obtain the 3-halogen-2-alkylphenol. The method has the advantages of high regioselectivity, good yield, simple operation flow and the like, and the purity of the obtained product can reach more than 99.5 percent.
The invention relates to a synthesis method of 3-halogen-2-alkylphenol, which comprises the following steps:
the method comprises the following steps: mixing the compound A with a catalyst of sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate and sulfolane, adding an inorganic base, reacting at a high temperature, and then adding palladium/carbon for catalytic hydrogenation to obtain 3-halogen-2-alkylphenol B;
the second method is as follows: and mixing the compound A, n-butyl bromide/chlorine and magnesium metal in an organic solvent, carrying out Grignard reagent exchange after initiation, then introducing air/oxygen for reaction, and obtaining the 3-halogen-2-alkylphenol B after hydrolysis.
The reaction equation is expressed as follows:
wherein: r is C1-C4 alkyl; x is halogen;
further, in the above technical scheme, in the method one, the inorganic base is selected from potassium hydroxide, sodium hydroxide, potassium tert-butoxide or sodium tert-butoxide, and the high temperature is selected from 100-120 ℃.
Further, in the above technical scheme, in the method one, the molar ratio of the compound a, the inorganic base and the dibenzyl alcohol is 1:1.05-1.48:1.01-1.22.
Further, in the technical scheme, in the first method, the palladium-carbon is 5% Pd/C or 10% Pd/C, the dosage is 3-20% of the weight of the compound A, and the hydrogenation pressure is 0.1-0.12Mpa.
Further, in the above technical scheme, the organic solvent of the second method is selected from tetrahydrofuran or 2-methyltetrahydrofuran.
Furthermore, in the technical scheme, the catalytic amount of tetraphenylporphyrin cobalt is added before the air/oxygen is introduced for reaction in the second method, and the addition amount is 0.01-0.03eq of the compound A, so that the oxidation can be accelerated.
Further, in the above technical scheme, in the second method, the ratio of the compound a, magnesium to n-butyl bromide/chlorine is 1:1.00-1.05:1.01-1.02.
Further, in the above technical scheme, the compound a preferably has the following structure:
for one mode of the method, compound 1 and compound 2 are preferably prepared. For the second mode of the process, compound 2, compound 3, compound 4 and compound 5 are preferably prepared. The corresponding structures of compounds 1-5 are as follows:
advantageous effects of the invention
1) 1, 3-dihalogen-2-toluene is used as a raw material, the over-high temperature is avoided during nucleophilic substitution, the reaction time is also greatly shortened, and dibenzyl alcohol reagent is adopted, so that one halogen is nucleophilic substituted, the other halogen is not easy to react, and the disubstituted impurity is reduced.
2) When halogen is chlorine or bromine, a Grignard reagent exchange mode is skillfully adopted, and the Grignard reagent is synthesized by n-butyl bromide and magnesium metal and simultaneously subjected to Grignard exchange with 1, 3-dihalogen-2-toluene; the method avoids the mode of diazonium salt/re-hydrolysis, reduces waste water and meets the development requirement of green chemistry.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
The invention is further illustrated by the following specific examples. These examples should be construed as merely illustrative of the present invention and not limiting the scope of the present invention. Various changes and modifications to the present invention may be made by one skilled in the art after reading the description herein, and such equivalent changes and modifications are intended to fall within the scope of the present invention as defined in the appended claims.
Synthesis of 3-fluoro-2-methylphenol, 3-chloro-2-methylphenol
Example 1
Under the protection of nitrogen, 25.6g (0.2 mol,1 eq) of 1, 3-difluorotoluene, 0.26g of sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate, 37.6g (0.204 mol,1.02 eq) of dibenzyl alcohol and 180mL of sulfolane are added into a reaction bottle, mixed, heated to 40 ℃, 11.76g (0.21 mol,1.05 eq) of KOH is added in batches, heated to 120 ℃ and stirred for reaction for 3 hours, cooled to room temperature, water and acetic acid are added to adjust pH=6.5-6.8, 200mL of methyl tertiary butyl ether are used for extraction, an organic phase is washed with saturated ammonium chloride and water, an organic phase is concentrated under reduced pressure, replaced by ethanol, 2.6g of 5% Pd/C is added, 0.1 is hydrogenated for 12 hours, pd/C is filtered through diatomite, 0.12g of thiobisphenol is added into filtrate, ethanol is evaporated under reduced pressure concentration, and high vacuum distillation is carried out to obtain 21.1g of 3-fluoro-2-methylphenol, 83.2%, and the yield is 99.7% by GC under high vacuum.
Example 2
Under the protection of nitrogen, 32.2g (0.2 mol,1 eq) of 1, 3-dichlorotoluene, 0.32g of tetra (3, 5-bis (trifluoromethyl) phenyl) sodium borate, 37.6g (0.204 mol,1.02 eq) of dibenzyl alcohol and 180mL of sulfolane are added into a reaction bottle, the mixture is mixed, the temperature is raised to 40 ℃, 20.2g (0.21 mol,1.05 eq) of sodium tert-butoxide is added in batches, the mixture is heated to 100 ℃ and stirred for reaction for 3 hours, the mixture is cooled to room temperature, water and acetic acid are added to adjust the pH to be 6.5-6.8, 200mL of methyl tert-butyl ether are used for extraction, an organic phase is washed by saturated ammonium chloride and water, an organic phase is concentrated under reduced pressure, ethanol is used for replacement, 3.2g of 5% Pd/C is added, 0.1Mpa is hydrogenated for 12 hours, 0.1g of thiobisphenol is added into filtrate, ethanol is distilled under reduced pressure, 25.4g of 3-chloro-2-methylphenol is obtained through distillation under high vacuum, 89.1% GC is obtained by GC99.5%.
Synthesis of 3-chloro-2-methylphenol, 3-chloro-2-ethylphenol, 3-bromo-2-methylphenol and 3-bromo-2-ethylphenol
Example 3
Under the protection of nitrogen, 3.0g of n-butyl chloride, 5g (0.21 mol,1.05 eq) of magnesium chips and 20mL of 2-methyltetrahydrofuran are added into a reaction bottle, the temperature is raised to 50 ℃, a plurality of iodine particles are added for initiation, then 300mL of 2-methyltetrahydrofuran solution containing 32.2g (0.2 mol,1.0 eq) of 1, 3-dichlorotoluene and 17.4g of n-butyl chloride is dropwise added at 55-60 ℃, the dropwise addition is finished, the reaction is carried out for 2 hours under heat preservation, and then the temperature is raised and the reflux reaction is carried out for 3 hours. Cooling to-25 ℃, introducing air to the pressure of 0.5Mpa in the kettle, reacting for 10 hours, adding 0.5M dilute hydrochloric acid to adjust the pH value to be 3-4, extracting with 200mL ethyl acetate, washing with saturated saline solution, adding 0.1g thiobisphenol into the organic phase, concentrating under reduced pressure, evaporating to remove the solvent, distilling under high vacuum to obtain 21.76g of 3-chloro-2-methylphenol, and obtaining the yield of 76.3% and GC 99.2%.
Example 4
Under the protection of nitrogen, 2.2g of 1-bromo-n-butane, 5g of magnesium dust (0.21 mol,1.05 eq) and 30mL of 2-methyltetrahydrofuran are added into a reaction bottle, the temperature is raised to 40 ℃, a plurality of iodine particles are added for initiation, then a solution of 280mL of 2-methyltetrahydrofuran containing 35.0g (0.2 mol,1.0 eq) of 1, 3-dichloro-ethylbenzene and 26.8g of 1-bromo-n-butane is dropwise added at 40-60 ℃, the dropwise addition is finished, the reaction is carried out for 2 hours under heat preservation, and then the temperature is raised for reflux reaction for 4 hours. Cooling to-25 ℃, introducing air to the pressure of 0.5Mpa in the kettle, reacting for 10 hours, adjusting the pH value to be 3-4 by 0.5M dilute hydrochloric acid, extracting by 200mL ethyl acetate, washing by saturated saline solution, adding 0.1g thiobisphenol into an organic phase, concentrating under reduced pressure, evaporating to remove the solvent, distilling under high vacuum to obtain 23.1g of 3-chloro-2-ethylphenol, and obtaining the product with the yield of 73.8% and GC of 99.5%.
Example 5
Under the protection of nitrogen, 3.0g of n-butyl chloride, 5g (0.21 mol,1.05 eq) of magnesium chips and 30mL of tetrahydrofuran are added into a reaction bottle, the temperature is raised to 50 ℃, a plurality of iodine particles are added for initiation, then, a solution of 50g (0.2 mol,1.0 eq) of 1, 3-dibromotoluene and 17.4g of n-butyl chloride in 330mL of tetrahydrofuran is added dropwise at 55-60 ℃, the dropwise addition is finished, the reaction is carried out for 2 hours under heat preservation, and then the temperature is raised and the reflux reaction is carried out for 4 hours. Cooling to-25 ℃, introducing air to the pressure of 0.5Mpa in the kettle, reacting for 10 hours, adding 0.5M dilute hydrochloric acid to adjust the pH value to be 3-4, extracting with 200mL ethyl acetate, washing with saturated saline solution, adding 0.1g thiobisphenol into the organic phase, concentrating under reduced pressure, evaporating the solvent, distilling under high vacuum to obtain 29.5g of 3-bromo-2-methylphenol, and obtaining the product with the yield of 78.8% and GC of 99.6%.
Example 6
Under the protection of nitrogen, 2.2g of 1-bromo-n-butane, 5g of magnesium chips (0.21 mol,1.05 eq) and 30mL of tetrahydrofuran are added into a reaction bottle, the temperature is raised to 40 ℃, a plurality of iodine particles are added for initiation, then a solution of 420mL of tetrahydrofuran containing 52.8g (0.2 mol,1.0 eq) of 1, 3-dibromoethylbenzene and 26.8g of 1-bromo-n-butane is added dropwise at 40-60 ℃, the dropwise addition is finished, the reaction is carried out for 2 hours under heat preservation, and then the temperature is raised and the reflux reaction is carried out for 4 hours. Cooling to-25 ℃, introducing air to the pressure of 0.5Mpa in the kettle, reacting for 10 hours, adjusting the pH value to be 3-4 by 0.5M dilute hydrochloric acid, extracting by 200mL ethyl acetate, washing by saturated saline solution, adding 0.1g thiobisphenol into an organic phase, concentrating under reduced pressure, evaporating to remove the solvent, distilling under high vacuum to obtain 28.75g of 3-bromo-2-ethylphenol, and obtaining the product with the yield of 71.5% and GC of 99.5%.
In the embodiment, after the Grignard exchange is completed, 0.003mol of tetraphenylporphyrin cobalt is added into the reaction system before air is introduced after the temperature is reduced to-25 ℃, the reaction time is 1.2 hours, the yield is 88.3 percent, and GC:99.1%.
The foregoing is only a preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art, who is within the scope of the present invention, should be covered by the protection scope of the present invention by making equivalents and modifications to the technical solution and the inventive concept thereof.
Claims (3)
1. The synthesis method of the 3-fluoro-2-methylphenol is characterized by comprising the following steps:
under the protection of nitrogen, 25.6g of 1, 3-difluorotoluene, 0.26g of sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate, 37.6g of dibenzyl alcohol and 180mL of sulfolane are added into a reaction bottle for mixing, the temperature is raised to 40 ℃, 11.76g of potassium hydroxide is added in batches, the temperature is raised to 120 ℃ for stirring reaction for 3 hours; cooling to room temperature, adding water and acetic acid to adjust pH=6.5-6.8, extracting with 200mL of methyl tertiary butyl ether, washing an organic phase with saturated ammonium chloride and water, concentrating the organic phase under reduced pressure, replacing with ethanol, adding 2.6g of 5% Pd/C, hydrogenating for 12 hours under 0.1Mpa, filtering Pd/C through kieselguhr, adding 0.12g of thiobisphenol into filtrate, concentrating under reduced pressure to evaporate ethanol, and distilling under high vacuum to obtain 21.1g of 3-fluoro-2-methylphenol with a yield of 83.2% and GC of 99.7%.
2. The synthesis method of the 3-chloro-2-methylphenol is characterized by comprising the following steps:
under the protection of nitrogen, adding 32.2g of 1, 3-dichlorotoluene, 0.32g of sodium tetrakis (3, 5-bis (trifluoromethyl) phenyl) borate, 37.6g of dibenzyl alcohol and 180mL of sulfolane into a reaction bottle, mixing, heating to 40 ℃, adding 20.2g of sodium tert-butoxide in batches, heating to 100 ℃, stirring and reacting for 3 hours; cooling to room temperature, adding water and acetic acid to adjust pH=6.5-6.8, extracting with 200mL of methyl tertiary butyl ether, washing an organic phase with saturated ammonium chloride and water, concentrating the organic phase under reduced pressure, replacing with ethanol, adding 3.2g of 5% Pd/C, hydrogenating for 12 hours under 0.1Mpa, filtering Pd/C through kieselguhr, adding 0.1g of thiobisphenol into filtrate, concentrating under reduced pressure to evaporate ethanol, distilling under high vacuum to obtain 25.4g of 3-chloro-2-methylphenol, and obtaining 89.1% yield and 99.5% GC.
3. The synthesis method of the 3-bromo-2-ethylphenol is characterized by comprising the following steps:
under the protection of nitrogen, adding 2.2g of 1-bromo-n-butane, 5g of magnesium chips and 30mL of tetrahydrofuran into a reaction bottle, heating to 40 ℃, adding a plurality of iodine to initiate, then dropwise adding 420mL of tetrahydrofuran solution containing 52.8g of 1, 3-dibromoethylbenzene and 26.8g of 1-bromo-n-butane at 40-60 ℃, keeping the temperature for 2 hours after the dropwise adding, and then heating and refluxing for 4 hours; cooling to-25 ℃, adding 0.003mol of tetraphenylporphyrin cobalt into a reaction system, introducing air to the pressure of 0.5Mpa in a kettle, reacting for 1.2 hours, adjusting the pH to 3-4 by 0.5M dilute hydrochloric acid, extracting by 200mL of ethyl acetate, washing by saturated saline, adding 0.1g of thiobisphenol into an organic phase, concentrating under reduced pressure, evaporating to remove a solvent, and distilling under high vacuum to obtain 3-bromo-2-ethylphenol, wherein the yield is 88.3% and GC 99.1%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111006568.0A CN113582818B (en) | 2021-08-30 | 2021-08-30 | Synthesis method of 3-halogen-2-alkylphenol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111006568.0A CN113582818B (en) | 2021-08-30 | 2021-08-30 | Synthesis method of 3-halogen-2-alkylphenol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113582818A CN113582818A (en) | 2021-11-02 |
| CN113582818B true CN113582818B (en) | 2023-08-01 |
Family
ID=78240349
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111006568.0A Active CN113582818B (en) | 2021-08-30 | 2021-08-30 | Synthesis method of 3-halogen-2-alkylphenol |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113582818B (en) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AP2007004047A0 (en) * | 2005-01-20 | 2007-06-30 | Pfizer Ltd | Substituted triazole derivatives as oxtocin antagonists |
| EP1893568A2 (en) * | 2005-06-07 | 2008-03-05 | Neurocrine Biosciences, Inc. | Monoamine re-uptake inhibitors and methods relating thereto |
| CN112645801A (en) * | 2020-12-27 | 2021-04-13 | 甘肃瀚聚药业有限公司 | Method for preparing o-fluorophenol by one-pot method |
-
2021
- 2021-08-30 CN CN202111006568.0A patent/CN113582818B/en active Active
Non-Patent Citations (2)
| Title |
|---|
| Process design methodology for organometallic chemistry in continuous flow systems;Hunter, Sarah M.等;Tetrahedron (2018);第74卷(第25期);3176-3182 * |
| 马祥志.有机化学.中国医药科技出版社,2014,226页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113582818A (en) | 2021-11-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2009526826A (en) | Process for producing substituted biphenyls | |
| CN113735701B (en) | Preparation method of 8-hydroxy-2,2,14,14-tetramethyl pentadecane diacid | |
| CN109400459B (en) | Preparation method of 2,4, 5-trifluoro-phenylacetic acid | |
| CN111484400B (en) | Preparation method of 2-methyl-4- (2,6, 6-trimethylcyclohexene-1-yl) -2-butenal | |
| CN105985248A (en) | Method for synthesizing amino biaromatic compound | |
| CN105237342A (en) | Method for preparing alcohol through catalytic hydrogenation reduction of carboxylate | |
| JP2010518134A (en) | Novel reaction with primary allyl alcohol | |
| CN113582818B (en) | Synthesis method of 3-halogen-2-alkylphenol | |
| CN105017099B (en) | Sitagliptin chiral intermediate and asymmetric synthesis method thereof | |
| CN110734368B (en) | Preparation method of buparvaquone | |
| CN108358783B (en) | 3-substituted glutaric diester and preparation method of glutaconic diester | |
| CN109761820B (en) | Chemical synthesis method of 3',4',5 '-trifluoro- [1,1' -biphenyl ] -2-amine | |
| CN108997117B (en) | Novel method for preparing 4-acetoxyl-2-methyl-2-butenal | |
| CN114249654B (en) | Process for preparing alkylanilines | |
| CN111087343A (en) | Hydroxypyridine ligand, preparation method and catalytic application thereof | |
| CN112209841B (en) | Synthesis method of terbutaline and application of terbutaline in preparation of terbutaline sulfate | |
| EP1326821A2 (en) | Method of making fluorinated alcohols | |
| CN113797976B (en) | Iridium catalyst for catalytic preparation of substituted ketone compound | |
| CN117417259A (en) | Separation method of trans-1, 2-cyclohexanediamine | |
| EP0805133B1 (en) | Process for cyclopentadiene substitution | |
| CN115888844A (en) | Palladium catalyst, preparation method and application thereof, and synthetic method of p-vinylbenzoic acid | |
| JPS61100551A (en) | Preparation of cycloalkylaminophenol derivative | |
| CN117142966A (en) | Efficient method for converting toremifene stereoisomer mixture | |
| CN117466695A (en) | Cobalt-catalyzed alkyne synthesis method | |
| GB2351735A (en) | Synthesis of (r)-1-(3,5-bis(trifluoromethyl)-phenyl)ethan-1-ol by asymmetric hydrogenation |
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 |