CN114702431A - Preparation method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane - Google Patents
Preparation method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane Download PDFInfo
- Publication number
- CN114702431A CN114702431A CN202210504202.4A CN202210504202A CN114702431A CN 114702431 A CN114702431 A CN 114702431A CN 202210504202 A CN202210504202 A CN 202210504202A CN 114702431 A CN114702431 A CN 114702431A
- Authority
- CN
- China
- Prior art keywords
- azabicyclo
- dimethyl
- hexane
- pressure
- reaction kettle
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
-
- 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
- Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
Abstract
The invention discloses a preparation method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane, which comprises the following steps: preparing caronic anhydride by adopting cis-caronic dicarboxylic acid; adding the caronic anhydride into a high-pressure reaction kettle, simultaneously injecting ammonia gas into the high-pressure reaction kettle, and sealing the high-pressure reaction kettle; heating and stirring the high-pressure reaction kettle to reach the temperature and pressure of supercritical ammonia, keeping the temperature and pressure for 120-150 min, cooling the high-pressure reaction kettle to 60-70 ℃, adding hot water, cooling, stirring, crystallizing for 1-2 h, performing suction filtration, washing and drying to obtain a compound A; reducing the compound A to obtain 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane; according to the invention, ammonia gas forms supercritical ammonia in a supercritical state to carry out ammonolysis reaction on the caronic anhydride, so that other solvents are not added, the ammonolysis effect can be improved, and the yield of the prepared product is higher.
Description
Technical Field
The invention relates to the technical field of preparation of medical intermediates, and relates to a preparation method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane.
Background
6, 6-dimethyl-3-azabicyclo [3.1.0] hexane is an important medical intermediate, is an important raw material used in the synthesis process of a plurality of medicaments such as hepatitis C protease inhibitor Boceprevir and oral medicament (PF-07321332) for treating new coronavirus, and is widely applied to other organic synthesis fields.
In the prior art, WO2008082508 reports a method for the synthesis of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane. Lithium aluminum hydride is used as a reducing agent, and then benzyl is removed by hydrogenation to prepare 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane. WO2007075790 reports another method for the synthesis of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane. The lithium aluminum hydride is also used for reduction, and then HCl gas is introduced at-23 to-20 ℃ for salt formation, but the purity of the final product is not mentioned in the literature. Meanwhile, the yield of the 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane obtained by the preparation method in the prior art is generally not high.
Disclosure of Invention
An object of the present invention is to solve at least the above problems and/or disadvantages and to provide at least the advantages described hereinafter.
To achieve these objects and other advantages in accordance with the present invention, there is provided a method for preparing 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane comprising the steps of:
step one, preparing caronic anhydride by using cis-caronic dicarboxylic acid;
adding the caronic anhydride into a high-pressure reaction kettle, injecting ammonia gas into the high-pressure reaction kettle, and sealing the high-pressure reaction kettle; heating and stirring the high-pressure reaction kettle to reach the temperature and pressure of supercritical ammonia, keeping the temperature and pressure for 120-150 min, cooling the high-pressure reaction kettle to 60-70 ℃, adding hot water, cooling, stirring, crystallizing for 1-2 h, performing suction filtration, washing and drying to obtain a compound A;
reducing the compound A to obtain 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane;
the structural formula of the compound A is as follows:
the structural formula of the 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane is as follows:
preferably, the process in the first step is as follows: adding cis-caron dicarboxylic acid and acetic anhydride into a supercritical carbon dioxide reactor, introducing carbon dioxide, stirring and reacting for 60-90 min at the temperature of 35-40 ℃ and the pressure of 10-15 MPa, decompressing, evaporating a solvent, adding methyl tert-butyl ether and petroleum ether at the temperature of 55-65 ℃, cooling to 0-10 ℃, stirring and crystallizing, filtering, and drying to obtain caron anhydride.
Preferably, the mass ratio of the cis-caron dicarboxylic acid to the acetic anhydride is 2-5: 6-8.
Preferably, in the second step, the molar ratio of the caronic anhydride to the ammonia gas is 1: 1-10.
Preferably, the temperature of the supercritical ammonia is 140-165 ℃ and the pressure is 5-25 MPa.
Preferably, in the second step, the temperature of the hot water is 50-60 ℃ and is reduced to 10-15 ℃.
Preferably, the process in step three is as follows: adding the compound A into toluene at room temperature, cooling to 0 ℃, dropwise adding a lithium aluminum hydride tetrahydrofuran solution, heating a reaction system to 40-50 ℃ after dropwise adding, reacting for 2-4 hours, cooling to room temperature, dropwise adding a dilute sodium hydroxide solution, quenching, adding water, layering, washing a water phase with ethyl acetate, combining organic phases, drying, concentrating a filtrate under reduced pressure to obtain a light yellow liquid compound, and performing reduced pressure rectification to obtain the compound, namely 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane.
The invention at least comprises the following beneficial effects: according to the invention, ammonia gas forms supercritical ammonia in a supercritical state to carry out ammonolysis reaction on the caronic anhydride, so that other solvents are not added, the ammonolysis effect can be improved, and the yield of the prepared product is higher.
Additional advantages, objects, and features of the invention will be set forth in part in the description which follows and in part will become apparent to those having ordinary skill in the art upon examination of the following or may be learned from practice of the invention.
The specific implementation mode is as follows:
the present invention is further described in detail below with reference to examples so that those skilled in the art can practice the invention with reference to the description.
It will be understood that terms such as "having," "including," and "comprising," as used herein, do not preclude the presence or addition of one or more other elements or groups thereof.
Example 1:
a method for preparing 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane comprising the steps of:
adding 98.6g of cis-caron dicarboxylic acid and 127.46g of acetic anhydride into a supercritical carbon dioxide reactor, introducing carbon dioxide, stirring and reacting for 60min at the temperature of 38 ℃ and the pressure of 12MPa, decompressing, evaporating a solvent, adding 200mL of methyl tert-butyl ether and 300mL of petroleum ether at the temperature of 60 ℃, cooling to 4 ℃, stirring and crystallizing, filtering, and drying at the temperature of 35 ℃ to obtain caron anhydride (yield is 87%);
adding 66g of caronic anhydride into a high-pressure reaction kettle, simultaneously injecting ammonia gas (the molar ratio of the caronic anhydride to the ammonia gas is 1:3) into the high-pressure reaction kettle, and sealing the high-pressure reaction kettle; heating and stirring the high-pressure reaction kettle to ensure that the temperature of the high-pressure reaction kettle reaches the supercritical ammonia condition is 145 ℃ and the pressure is 12MPa, preserving heat and maintaining pressure for 120min, cooling the high-pressure reaction kettle to 70 ℃, relieving pressure, adding hot water at 60 ℃, cooling, stirring and crystallizing for 2h, performing suction filtration, washing with ice water, and drying at 45 ℃ to obtain a compound A (yield is 92%);
the structural formula of the compound A is as follows:
step three, adding 22g of compound A and 280mL of tetrahydrofuran into a three-necked flask at room temperature, cooling to 0 ℃, dropwise adding 350mL of 1M lithium aluminum hydride tetrahydrofuran solution, heating the reaction system to 45 ℃ after dropwise adding, reacting for 3 hours, cooling to room temperature, dropwise adding dilute sodium hydroxide solution, quenching, adding 50mL of water, layering, washing the aqueous phase with ethyl acetate (100mL multiplied by 2), combining the organic phase and anhydrous Na2SO4Drying, concentrating the filtrate under reduced pressure to obtain light yellow liquid compound, and rectifying under reduced pressure to obtain 6, 6-dimethyl-3-azabicyclo [3.1.0]]Hexane (yield 89%);
the structural formula of the 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane is as follows:
example 2:
a method for preparing 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane comprising the steps of:
adding 98.6g of cis-caron dicarboxylic acid and 127.46g of acetic anhydride into a supercritical carbon dioxide reactor, introducing carbon dioxide, stirring and reacting for 60min at the temperature of 40 ℃ and the pressure of 15MPa, decompressing, evaporating a solvent, adding 200mL of methyl tert-butyl ether and 300mL of petroleum ether at the temperature of 60 ℃, cooling to 4 ℃, stirring and crystallizing, filtering, and drying at the temperature of 35 ℃ to obtain caron anhydride (yield is 88%); the reaction is carried out in the supercritical carbon dioxide, so that the addition of an extra solvent can be avoided, the preparation effect of the anhydride can be improved, the reaction is more thorough, and the yield of the prepared product is higher;
adding 66g of caronic anhydride into a high-pressure reaction kettle, simultaneously injecting ammonia gas (the molar ratio of the caronic anhydride to the ammonia gas is 1:3) into the high-pressure reaction kettle, and sealing the high-pressure reaction kettle; heating and stirring a high-pressure reaction kettle to ensure that the temperature of the high-pressure reaction kettle reaches the supercritical ammonia condition is 150 ℃ and the pressure is 18MPa, preserving heat and pressure for 120min, cooling the high-pressure reaction kettle to 70 ℃, relieving pressure, adding hot water at 60 ℃, cooling, stirring and crystallizing for 2h, performing suction filtration, washing with ice water, and drying at 45 ℃ to obtain a compound A (yield of 91%);
the structural formula of the compound A is as follows:
step three, adding 22g of compound A and 280mL of tetrahydrofuran into a three-necked bottle at room temperature, cooling to 0 ℃, dropwise adding 350mL of 1M lithium aluminum hydride tetrahydrofuran solution, heating the reaction system to 45 ℃ after dropwise adding, and reactingAllowing for 3 hr, cooling to room temperature, adding diluted sodium hydroxide solution, quenching, adding 50mL water, separating layers, washing water phase with ethyl acetate (100mL × 2), combining organic phase, anhydrous Na2SO4Drying, concentrating the filtrate under reduced pressure to obtain light yellow liquid compound, and rectifying under reduced pressure to obtain 6, 6-dimethyl-3-azabicyclo [3.1.0]]Hexane (yield 90%); the 6, 6-dimethyl-3-azabicyclo [3.1.0]The structural formula of hexane is:
comparative example 1:
a method for preparing 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane comprising the steps of:
step one, adding 98.6g of cis-caro dicarboxylic acid and 127.46g of acetic anhydride into a three-necked bottle, stirring and reacting for 60min at room temperature, evaporating out the solvent, adding 200mL of methyl tert-butyl ether and 300mL of petroleum ether at 60 ℃, cooling to 4 ℃, stirring and crystallizing, filtering, and drying at 35 ℃ to obtain caro anhydride (yield is 65%);
adding 66g of caronic anhydride into a high-pressure reaction kettle, simultaneously injecting ammonia gas (the molar ratio of the caronic anhydride to the ammonia gas is 1:3) into the high-pressure reaction kettle, and sealing the high-pressure reaction kettle; stirring the high-pressure reaction kettle at room temperature for 120min, adding hot water at 60 ℃, cooling, stirring and crystallizing for 2h, carrying out suction filtration, washing with ice water, and drying at 45 ℃ to obtain a compound A (yield is 70%);
step three, adding 22g of compound A and 280mL of tetrahydrofuran into a three-necked flask at room temperature, cooling to 0 ℃, dropwise adding 350mL of 1M lithium aluminum hydride tetrahydrofuran solution, heating the reaction system to 45 ℃ after dropwise adding, reacting for 3 hours, cooling to room temperature, dropwise adding dilute sodium hydroxide solution, quenching, adding 50mL of water, layering, washing the aqueous phase with ethyl acetate (100mL multiplied by 2), combining the organic phase and anhydrous Na2SO4Drying, concentrating the filtrate under reduced pressure to obtain light yellow liquid compound, and rectifying under reduced pressure to obtain 6, 6-dimethyl-3-azabicyclo [3.1.0]]Hexane (yield 78%). Comparative example 1 was carried out without using supercritical carbon dioxide and supercritical ammoniaThe yield of the product is low, and the final product 6, 6-dimethyl-3-azabicyclo [3.1.0] is caused by the problems of incomplete reaction and impure product]The yield of hexane decreased significantly.
While embodiments of the invention have been described above, it is not limited to the applications set forth in the description and the embodiments, which are fully applicable to various fields of endeavor for which the invention may be embodied with additional modifications as would be readily apparent to those skilled in the art, and the invention is therefore not limited to the details given herein and to the examples shown and described without departing from the generic concept as defined by the claims and their equivalents.
Claims (7)
1. A process for the preparation of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane comprising the steps of:
step one, preparing caronic anhydride by adopting cis-caronic dicarboxylic acid;
adding the caronic anhydride into a high-pressure reaction kettle, injecting ammonia gas into the high-pressure reaction kettle, and sealing the high-pressure reaction kettle; heating and stirring the high-pressure reaction kettle to reach the temperature and pressure of supercritical ammonia, keeping the temperature and pressure for 120-150 min, cooling the high-pressure reaction kettle to 60-70 ℃, adding hot water, cooling, stirring, crystallizing for 1-2 h, performing suction filtration, washing and drying to obtain a compound A;
reducing the compound A to obtain 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane;
the structural formula of the compound A is as follows:
the structural formula of the 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane is as follows:
2. the method of claim 1, wherein the process in step one comprises: adding cis-caron dicarboxylic acid and acetic anhydride into a supercritical carbon dioxide reactor, introducing carbon dioxide, stirring and reacting for 60-90 min at the temperature of 35-40 ℃ and the pressure of 10-15 MPa, decompressing, evaporating a solvent, adding methyl tert-butyl ether and petroleum ether at the temperature of 55-65 ℃, cooling to 0-10 ℃, stirring and crystallizing, filtering, and drying to obtain caron anhydride.
3. The method for producing 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane as claimed in claim 2 wherein the mass ratio of cis-caron dicarboxylic acid to acetic anhydride is 2-5: 6-8.
4. The method for producing 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane according to claim 1, wherein in the second step, the molar ratio of the caronic anhydride to the ammonia gas is 1:1 to 10.
5. The method for producing 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane according to claim 1, wherein the supercritical ammonia is at a temperature of 140 to 165 ℃ and a pressure of 5 to 25 MPa.
6. The method for preparing 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane according to claim 1, wherein in the second step, the temperature of the hot water is 50-60 ℃ and the temperature is reduced to 10-15 ℃.
7. The process for the preparation of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane, according to claim 1, wherein the process in step three is: adding the compound A into toluene at room temperature, cooling to 0 ℃, dropwise adding a lithium aluminum hydride tetrahydrofuran solution, heating a reaction system to 40-50 ℃ after dropwise adding, reacting for 2-4 hours, cooling to room temperature, dropwise adding a dilute sodium hydroxide solution, quenching, adding water, layering, washing a water phase with ethyl acetate, combining organic phases, drying, concentrating a filtrate under reduced pressure to obtain a light yellow liquid compound, and rectifying under reduced pressure to obtain the compound, namely 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210504202.4A CN114702431B (en) | 2022-05-10 | 2022-05-10 | Preparation method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210504202.4A CN114702431B (en) | 2022-05-10 | 2022-05-10 | Preparation method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114702431A true CN114702431A (en) | 2022-07-05 |
| CN114702431B CN114702431B (en) | 2023-06-23 |
Family
ID=82177518
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210504202.4A Active CN114702431B (en) | 2022-05-10 | 2022-05-10 | Preparation method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114702431B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115108962A (en) * | 2022-08-01 | 2022-09-27 | 上海巽田科技股份有限公司 | Method for continuously synthesizing azabicyclo compound |
| CN115197119A (en) * | 2022-09-01 | 2022-10-18 | 江苏科本药业有限公司 | Preparation method of 6,6-dimethyl-3-azabicyclo [3.1.0] hexane-2,4-diketone |
| CN115232059A (en) * | 2022-08-01 | 2022-10-25 | 上海巽田科技股份有限公司 | Synthetic method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58167581A (en) * | 1982-03-29 | 1983-10-03 | Ueno Seiyaku Oyo Kenkyusho:Kk | Production of bicyclolactone |
| CN101020680A (en) * | 2006-05-17 | 2007-08-22 | 沈阳感光化工研究院 | Synthesis process of 6,6-dimethyl-3-oxo dicyclo [3,1,0]-hexane-2,4-dione |
| US20090240063A1 (en) * | 2005-12-22 | 2009-09-24 | George Wu | Process For The Preparation Of 6,6-Dimethyl-3-Azabicyclo-[3.1.0]-Hexane Compounds ... |
| CN102952011A (en) * | 2011-08-24 | 2013-03-06 | 上海北卡医药技术有限公司 | New synthetic method of carane aldehyde acid lactone, caronic acid, caronic anhydride and key intermediates thereof |
| CN103435532A (en) * | 2013-09-02 | 2013-12-11 | 苏州永健生物医药有限公司 | Synthetic method of boceprevir intermediate |
| CN103864672A (en) * | 2012-12-18 | 2014-06-18 | 上海迪赛诺化学制药有限公司 | Method for preparing (1S, 5S)-6,6-dimethyl-3-azabicyclo [3.1.0] hexane-2-carboxylic acid alkyl ester |
| CN105330589A (en) * | 2015-11-16 | 2016-02-17 | 江苏大学 | Preparation method of boceprevir intermediate |
| CN113999160A (en) * | 2021-10-21 | 2022-02-01 | 江苏省药物研究所有限公司 | Preparation method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane |
| CN114105859A (en) * | 2022-01-27 | 2022-03-01 | 南京桦冠生物技术有限公司 | Synthetic method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane |
-
2022
- 2022-05-10 CN CN202210504202.4A patent/CN114702431B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58167581A (en) * | 1982-03-29 | 1983-10-03 | Ueno Seiyaku Oyo Kenkyusho:Kk | Production of bicyclolactone |
| US20090240063A1 (en) * | 2005-12-22 | 2009-09-24 | George Wu | Process For The Preparation Of 6,6-Dimethyl-3-Azabicyclo-[3.1.0]-Hexane Compounds ... |
| CN101020680A (en) * | 2006-05-17 | 2007-08-22 | 沈阳感光化工研究院 | Synthesis process of 6,6-dimethyl-3-oxo dicyclo [3,1,0]-hexane-2,4-dione |
| CN102952011A (en) * | 2011-08-24 | 2013-03-06 | 上海北卡医药技术有限公司 | New synthetic method of carane aldehyde acid lactone, caronic acid, caronic anhydride and key intermediates thereof |
| CN103864672A (en) * | 2012-12-18 | 2014-06-18 | 上海迪赛诺化学制药有限公司 | Method for preparing (1S, 5S)-6,6-dimethyl-3-azabicyclo [3.1.0] hexane-2-carboxylic acid alkyl ester |
| CN103435532A (en) * | 2013-09-02 | 2013-12-11 | 苏州永健生物医药有限公司 | Synthetic method of boceprevir intermediate |
| CN105330589A (en) * | 2015-11-16 | 2016-02-17 | 江苏大学 | Preparation method of boceprevir intermediate |
| CN113999160A (en) * | 2021-10-21 | 2022-02-01 | 江苏省药物研究所有限公司 | Preparation method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane |
| CN114105859A (en) * | 2022-01-27 | 2022-03-01 | 南京桦冠生物技术有限公司 | Synthetic method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane |
Non-Patent Citations (3)
| Title |
|---|
| 无作者: "酸酐的化学反应", 《豆丁网》 * |
| 无作者: "酸酐的化学反应", 《豆丁网》, 11 June 2016 (2016-06-11), pages 1 * |
| 汪多仁: "超临界CO2的开发与应用进展", 染整技术, vol. 33, no. 9, pages 37 - 43 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115108962A (en) * | 2022-08-01 | 2022-09-27 | 上海巽田科技股份有限公司 | Method for continuously synthesizing azabicyclo compound |
| CN115232059A (en) * | 2022-08-01 | 2022-10-25 | 上海巽田科技股份有限公司 | Synthetic method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane |
| CN115232059B (en) * | 2022-08-01 | 2023-11-21 | 上海巽田科技股份有限公司 | Synthesis method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane |
| CN115108962B (en) * | 2022-08-01 | 2024-03-19 | 上海巽田科技股份有限公司 | Method for continuously synthesizing azabicyclo compound |
| CN115197119A (en) * | 2022-09-01 | 2022-10-18 | 江苏科本药业有限公司 | Preparation method of 6,6-dimethyl-3-azabicyclo [3.1.0] hexane-2,4-diketone |
| CN115197119B (en) * | 2022-09-01 | 2024-01-16 | 江苏科本药业有限公司 | Preparation method of 6,6-dimethyl-3-azabicyclo [3.1.0] hexane-2, 4-dione |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114702431B (en) | 2023-06-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114702431A (en) | Preparation method of 6, 6-dimethyl-3-azabicyclo [3.1.0] hexane | |
| WO2017096772A1 (en) | Method for preparing anti-heart-failure medicine lcz696 | |
| CN114940643B (en) | Synthesis method of medical hydroquinone | |
| CN110845443B (en) | Method for preparing high-purity tolperisone hydrochloride | |
| CN112479906A (en) | Production process of meglumine | |
| CN110256397A (en) | The extracting method of biuret during urea and polyol reaction cyclic carbonate | |
| CN113956173B (en) | Preparation method of tranexamic acid | |
| CN111116430B (en) | Preparation method of sodium taurate | |
| CN112645799B (en) | Resorcinol post-treatment process | |
| CN114835661A (en) | Industrial preparation method of a-acetyl-r-butyrolactone | |
| CN112661672A (en) | Crystallization method of Boc-amino acid | |
| CN109293524B (en) | Preparation method of high-purity diacetone acrylamide | |
| CN111100010A (en) | Preparation method of p-fluorobenzylamine | |
| CN111039917A (en) | Preparation method of 1, 4-cyclohexanedione mono-ketal | |
| CN115232015B (en) | Synthesis method of chloroquine chiral side chain | |
| CN115340510B (en) | Preparation method of brivaracetam intermediate | |
| CN117263807B (en) | Dialkyl dimethyl ammonium chloride and preparation method thereof | |
| CN112375031B (en) | Preparation method of cilnidipine | |
| CN114478338B (en) | Preparation method of high-purity alpha-methylthio acetoxime | |
| CN115466255B (en) | Tropine and synthetic method thereof | |
| CN117142933A (en) | Preparation method of 1, 3-cyclohexanedione sodium salt | |
| CN118290280A (en) | Method for synthesizing tranexamic acid under mild oxidation condition | |
| CN110183355B (en) | Refining method of high-purity o-chloro mandelonitrile | |
| CN116120395A (en) | Preparation method of Nemactetvir intermediate | |
| CN115109026A (en) | Preparation method of levalbuterol intermediate and hydrochloride with high ee value |
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 |