CN112250594B - Method for preparing 3-acetamido-1-adamantanol - Google Patents
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- C07—ORGANIC CHEMISTRY
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- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
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- C—CHEMISTRY; METALLURGY
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Abstract
The invention discloses a method for preparing 3-acetamido-1-adamantanol, which belongs to the technical field of chemical synthesis, and the process uses adamantane as a starting material, acetonitrile is added into fuming sulfuric acid for amidation reaction, and HNO is used for the amidation reaction 3 Nitration, KOH/H 2 O alkaline hydrolysis reaction and separation and purification process to obtain 3-acetamido-1-adamantanol. The method for preparing the 3-acetamido-1-adamantanol by adopting the sulfuric acid system continuous utilization method reduces the production of waste acid, is environment-friendly, low in raw material price, quick in reaction, high in yield, high in purity, simple in process and suitable for industrial production.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and relates to a method for preparing 3-acetamido-1-adamantanol.
Background
Vildagliptin is a highly selective, competitive and reversible DPP-IV inhibitor developed by North China pharmaceutical company, and can effectively control blood sugar in clinic when being used alone or in combination with other antidiabetic medicines. In 2008, vildagliptin is marketed in europe, and in 2011, the vildagliptin enters the china market under the trade name "jiavile", and is marketed in many countries in the world at present, so that the vildagliptin has a better development prospect.
By performing a reverse synthetic analysis on vildagliptin, 3-amino-1-adamantanol is a key intermediate for synthesizing vildagliptin, and 3-acetamido-1-adamantanol is an intermediate for synthesizing 3-amino-1-adamantanol.
In the prior art, 3-amino-1-adamantanol is used as a raw material to react with acetyl chloride, or 3-amino-1-adamantanol is used as a raw material to react with acetic anhydride in tetrahydrofuran solvent to prepare 3-acetamido-1-adamantanol, a large amount of waste acid is generated in the reaction process, and the reaction starting materials are expensive.
At present, 1-acetamido adamantane is used as a raw material to prepare 3-acetamido-1-adamantanol by culturing cyclosporin in N, N-dimethylformamide at 23 ℃ for 150 hours, and the yield is 16%; or 1-acetamido adamantane is used as a raw material to react with 1, 4-dihydro nicotinamide adenine dinucleotide, the pavilion pradaprotein reductase and P450cam in ethanol with the temperature of 25 ℃ for 1.5 hours to prepare 3-acetamido-1-adamantanol, wherein the yield is 15%; or 1-acetamido adamantane is used as a raw material, reacts with acetic acid and nitric acid mixed acid system, and then is put into water containing urea to react to prepare the 3-acetamido-1-adamantanol, and the yield of the product is 26%.
Therefore, the existing reaction starting materials for preparing the 3-acetamido-1-adamantanol are expensive, a large amount of waste acid is generated in the reaction process, the yield is low, and the method is not suitable for industrial production.
Disclosure of Invention
The invention aims to solve the problems that a large amount of waste acid is generated in the process of preparing 3-acetamido-1-adamantanol, raw materials are expensive and the method is not suitable for large-scale production in the prior art, and provides a method for preparing 3-acetamido-1-adamantanol.
In order to solve the technical problems, the invention provides a synthesis method for synthesizing 3-acetamido-1-adamantanolThe method comprises the following steps: step A, amidation reaction: under the conditions of ice water bath and stirring, the SO is added 3 Adding adamantane into fuming sulfuric acid with the mass fraction of 10% -30%, dropwise adding acetonitrile, controlling the temperature of a reaction system to be not more than 20 ℃, and reacting under normal temperature after the dropwise adding is completed to obtain a reaction solution containing 1-acetamido adamantane; step B, nitration reaction: adding nitric acid into the reaction solution containing 1-acetamido adamantane prepared in the step A under the conditions of ice-water bath and stirring, controlling the reaction temperature to be 0-10 ℃, reacting for 1-3 hours, and then reacting at normal temperature to obtain the reaction solution containing 3-nitro-1-acetamido adamantane; step C, alkaline hydrolysis reaction: under the condition of ice water bath, the reaction liquid containing 3-nitro-1-acetamido adamantane prepared in the step B is added into a reaction vessel filled with crushed ice, the temperature of the reaction system is controlled to be not more than 50 ℃, and the pH value of the reaction liquid is regulated by alkali>12, transferring to ice water bath condition, reacting for 1-3 hours, standing at normal temperature, reacting, and separating solid from liquid to obtain liquid and solid containing 3-acetamido-1-adamantanol.
After the amidation process of step a, the prior art adds a large amount of saturated sodium chloride solution to the system for salting out, and uses methylene dichloride to extract the intermediate 1-acetamido adamantane, thereby generating a large amount of waste acid which is difficult to treat. The invention uses the original sulfuric acid in the step A as the solvent in the nitration reaction of the step B directly, and nitric acid is directly added for mixed acid nitration, and side reaction can not be generated. Fuming nitric acid may also be used in the present invention for nitration.
As a preferred technical scheme, the present invention further includes a step of purifying the 3-acetamido-1-adamantanol-containing liquid and solid prepared in step C, including: step a: adjusting the pH of the liquid containing 3-acetamido-1-adamantanol prepared in the step C to 5-10 by using acid A, concentrating the liquid to be powdery, adding the solvent A, heating and refluxing, placing under ice water bath, carrying out solid-liquid separation, and collecting the liquid A; step b: c, dissolving the solid containing 3-acetamido-1-adamantanol prepared in the step C by using a solvent A, heating and refluxing, then placing under ice water bath, separating solid from liquid, and collecting a liquid B; step c: mixing the liquid A and the liquid B, concentrating to powder, adding the obtained powder into the solvent B, heating and refluxing, and carrying out solid-liquid separation to obtain 3-acetamido-1-adamantanol solid; the solvent A is selected from one of absolute ethyl alcohol, methanol, tetrahydrofuran and dichloromethane, preferably the absolute ethyl alcohol; the solvent B is selected from one of acetone, ethyl acetate and n-hexane, preferably acetone; the acid A is one selected from hydrochloric acid, sulfuric acid and phosphoric acid, preferably hydrochloric acid.
As a preferable technical scheme, SO in the step A is obtained 3 The fuming sulfuric acid with the mass fraction of 10-30% is 5-10 times of the amount of adamantane; if the amount of fuming sulfuric acid is increased, unnecessary environmental pollution is generated, and if the amount of fuming sulfuric acid is further reduced, incomplete reaction is caused.
As a preferable technical scheme, the acetonitrile dosage in the step A is 1-3 times of the adamantane substance dosage, and the reaction time at the normal temperature is 1-3 hours.
As a preferred technical scheme, the amount of nitric acid in the step B is 1-3 times of the amount of adamantane substance, wherein the nitric acid is selected from one of fuming nitric acid and concentrated nitric acid, and preferably concentrated nitric acid; the reaction time is 1-3 hours at normal temperature.
As a preferable technical scheme, the reaction time at normal temperature in the step B is 1-3 hours.
As a preferred embodiment, the base in the step C is selected from one of potassium hydroxide and sodium hydroxide, preferably potassium hydroxide; the reaction time is 1-3 hours at normal temperature.
As a preferable technical scheme, the dosage of the solvent A in the step a and the step b is 10-15 times of the dosage of adamantane substances respectively, the reflux temperature is 50-75 ℃, the reflux time is 1-2 hours, and the standing time is 0.5-2 hours under the ice water bath condition.
As a preferable technical scheme, the dosage of the solvent B in the step c is 1-2 times of the dosage of adamantane substances, the reflux temperature is 40-50 ℃, and the reflux time is 1-2 hours.
As a preferred technical scheme, the above-mentioned step of purifying the 3-acetamido-1-adamantanol-containing liquid and solid prepared in step C includes: step a: adjusting the pH of the liquid containing 3-acetamido-1-adamantanol prepared in the step C to 7-8 by using hydrochloric acid, concentrating the liquid to be powdery, adding absolute ethyl alcohol, wherein the dosage of the absolute ethyl alcohol is 10 times that of adamantane substances, heating to 75 ℃ and refluxing for 1.5 hours, standing under an ice water bath for 1 hour, carrying out solid-liquid separation, and collecting liquid A; step b: dissolving the solid containing 3-acetamido-1-adamantanol prepared in the step C with absolute ethyl alcohol, wherein the dosage of the absolute ethyl alcohol is 10 times that of adamantane substances, heating to 75 ℃ and refluxing for 1.5 hours, standing for 1 hour under an ice water bath, carrying out solid-liquid separation, and collecting liquid B; step c: mixing the liquid A and the liquid B, concentrating to obtain powder, adding the obtained powder into an acetone solvent, wherein the dosage of acetone is 1.5 times of that of adamantane substances, heating to 45 ℃ and refluxing for 1.5 hours, and carrying out solid-liquid separation to obtain 3-acetamido-1-adamantanol solid, and the yield is more than or equal to 85%.
The above process of extracting the product with absolute ethanol results in a sharp decrease in the amount of the product extracted with absolute ethanol if the pH is not adjusted with hydrochloric acid or if the pH is adjusted with an excessive amount of hydrochloric acid.
Compared with the prior art, the invention has the advantages that: (1) The invention uses adamantane as raw material, is simple and easy to obtain, has low price, and greatly reduces the cost of industrial production; (2) The invention greatly reduces the usage amount of sulfuric acid, reduces the production of waste acid, is environment-friendly and reduces the cost; (3) The product obtained by the invention has high yield and high purity, and is suitable for large-scale production.
Drawings
FIG. 1 is a synthetic route diagram of the present invention.
Detailed Description
The invention is further described below with reference to the accompanying drawings.
A process for preparing 3-acetamido-1-adamantanol as shown in figure 1 comprising the steps of: step A, amidation reaction; step B, nitration reaction; step C, alkaline hydrolysis reaction; and D, purifying.
The normal temperature in the invention means that the temperature range is 20-30 ℃.
The concentrated nitric acid in the invention adopts commercial concentrated nitric acid, the mass fraction is about 68%, the density is about 1.4g/cm, and the boiling point is 83 ℃.
Example 1: step A, amidation reaction: under ice water bath conditions, 40ml of SO was added to a four-necked flask 3 Adding 4g of adamantane under stirring, slowly adding 4ml of acetonitrile after the adamantane is completely dissolved, controlling the temperature of a reaction system to be not more than 20 ℃, transferring the system to normal temperature after adding, and reacting for 3 hours to obtain a reaction solution containing 1-acetamido adamantane.
Step B, nitration reaction: and D, dropwise adding 4ml of 65% concentrated nitric acid into the reaction solution containing the 1-acetamido adamantane prepared in the step A under the conditions of ice-water bath and stirring, controlling the reaction temperature to be 0-10 ℃, reacting for 1.5 hours, and reacting for 1.5 hours at normal temperature to obtain the reaction solution containing the 3-nitro-1-acetamido adamantane.
Step C, alkaline hydrolysis reaction: and B, putting 80g of crushed ice into another four-neck flask, slowly adding the reaction solution containing 3-nitro-1-acetamido adamantane prepared in the step B into the crushed ice under the conditions of ice water bath and stirring, controlling the temperature of the system to be not more than 50 ℃, keeping the ice water bath condition, slowly adding potassium hydroxide solid, regulating the pH of the solution to be more than 12, generating a large amount of white thick solid, keeping the ice water bath condition for reaction for 1 hour, removing the ice water bath, continuing the reaction for 1 hour, and carrying out suction filtration to obtain filtrate and filter cake.
Step D, purification: separating the filtrate obtained in the step C from the filter cake, regulating the pH of the filtrate to 7 by using hydrochloric acid, concentrating the filtrate to be powdery, adding 60ml of absolute ethyl alcohol, heating and refluxing for 1 hour at 65 ℃, transferring to an ice water bath, standing for 30min, carrying out suction filtration, and concentrating the filtrate to be powdery to obtain a solid A; directly using 60ml of absolute ethyl alcohol for heating and refluxing for 1 hour at 65 ℃, transferring to an ice water bath, standing for 30min, carrying out suction filtration, concentrating filtrate to obtain a powder form to obtain a solid B, combining the solid A and the solid B, using 10ml of acetone solution to heat and reflux the powder, carrying out suction filtration, discarding the filtrate, and drying the filter cake to obtain 5.18g of 3-acetamido-1-adamantanol, wherein the purity is 97%, and the yield is 84.3%.
Example 2: step A, amidation reaction: under ice water bath conditions, 40ml of SO was poured into a four-necked flask 3 And (3) adding 8g of adamantane under stirring, slowly adding 8ml of acetonitrile after the adamantane is completely dissolved, controlling the temperature of a reaction system to be not more than 20 ℃, transferring the system to normal temperature for reaction for 1 hour after the addition, and obtaining a reaction solution containing 1-acetamido adamantane.
Step B, nitration reaction: and (3) adding 15ml of fuming nitric acid into the reaction solution containing the 1-acetamido adamantane prepared in the step (A) under the conditions of ice water bath and stirring, reacting for 1 hour under the condition of ice water bath after the addition, and then reacting for 1 hour at normal temperature to obtain the reaction solution containing the 3-nitro-1-acetamido adamantane.
Step C, alkaline hydrolysis reaction: and C, putting 80g of crushed ice into another four-neck flask, transferring to an ice water bath, slowly adding the reaction solution containing 3-nitro-1-acetamido adamantane prepared in the step B into the crushed ice under the stirring condition, controlling the temperature of the system to be not more than 50 ℃, keeping the ice water bath condition, slowly adding sodium hydroxide solid, regulating the pH of the solution to be more than 12, generating a large amount of white thick solid, keeping the ice water bath condition for reaction for 2 hours, removing the ice water bath, continuing the reaction for 2 hours, and carrying out suction filtration to obtain filtrate and filter cake. .
Step D, purification: separating filtrate and filter cake, adjusting pH of filtrate to 10 with hydrochloric acid, concentrating filtrate to powder, adding 120ml of absolute ethanol, heating and refluxing at 75deg.C for 2 hr, transferring to ice water bath, standing for 30min, suction filtering, and concentrating filtrate to powder to obtain solid A; directly using 100ml of absolute ethyl alcohol for the filter cake, heating and refluxing for 2 hours at the temperature of 75 ℃, transferring to an ice water bath, standing for 30 minutes, carrying out suction filtration, and concentrating the filtrate to be powdery to obtain a solid B; the solid A and the solid B were combined, and the powder was heated under reflux using 20ml of a solution of acetone, suction-filtered, the filtrate was removed, and the cake was dried to give 9.98g of 3-acetamido-1-adamantanol, 95% pure and 81.2% yield.
Example 3: step A, amidation process:under ice water bath conditions, 60ml of SO was poured into a four-necked flask 3 And (3) adding 8g of adamantane under stirring, slowly adding 16ml of acetonitrile after the adamantane is completely dissolved, controlling the temperature of a reaction system to be not more than 20 ℃, transferring the system to normal temperature for reaction for 1.5 hours after the addition, and obtaining a reaction solution containing 1-acetamido adamantane.
Step B, nitrifying: and (3) adding 10ml of fuming nitric acid into the reaction solution containing the 1-acetamido adamantane prepared in the step (A) under the conditions of ice water bath and stirring, controlling the reaction temperature to be 0-10 ℃, reacting for 1.5 hours under the ice water bath condition, and then reacting for 1.5 hours at normal temperature to obtain the reaction solution containing the 3-nitro-1-acetamido adamantane.
Step C, alkaline hydrolysis: and C, putting 120g of crushed ice into another four-neck flask, transferring to an ice water bath, slowly adding the reaction solution containing 3-nitro-1-acetamido adamantane prepared in the step B into the crushed ice under the stirring condition, controlling the temperature of the system to be not more than 50 ℃, keeping the ice water bath condition, slowly adding sodium hydroxide solid, regulating the pH of the solution to be more than 12, generating a large amount of white thick solid, keeping the ice water bath condition for reaction for 2 hours, removing the ice water bath, continuing the reaction for 1.5 hours, and carrying out suction filtration to obtain filtrate and filter cake.
Step D, purification: separating filtrate and filter cake, regulating pH of filtrate to 5 with hydrochloric acid, concentrating filtrate to powder, adding 100ml of anhydrous ethanol, heating and refluxing at 75deg.C for 2 hr, transferring to ice water bath, standing for 30min, suction filtering, and concentrating filtrate to powder to obtain solid A; directly using 100ml of absolute ethyl alcohol for the filter cake, heating and refluxing for 2 hours at the temperature of 75 ℃, transferring to an ice water bath, standing for 30 minutes, carrying out suction filtration, and concentrating the filtrate to be powdery to obtain a solid B; the solid A and the solid B were combined together, and the powder was heated under reflux using 30ml of a solution of acetone, suction-filtered, the filtrate was removed, and the cake was dried to give 10.12g of 3-acetamido-1-adamantanol with a purity of 95% and a yield of 82.3%.
While the embodiments of the present invention have been described in detail with reference to a large number of experimental data, the present invention is not limited to the above data, and it will be apparent to those skilled in the art that some reasonable changes may be made to the technical solutions of the present invention without departing from the spirit and scope of the present invention, and the present invention also falls within the scope of protection of the present invention.
Claims (3)
1. A process for preparing 3-acetamido-1-adamantanol, comprising the steps of:
step A, amidation reaction: under the ice water bath condition, adding 40ml of fuming sulfuric acid with the mass fraction of SO3 of 10 percent into a four-neck flask, adding 4g of adamantane under the stirring condition, slowly adding 4ml of acetonitrile after the adamantane is completely dissolved, controlling the temperature of a reaction system to be not more than 20 ℃, transferring the system to normal temperature for reaction for 3 hours after the addition, and obtaining a reaction solution containing 1-acetamido adamantane;
step B, nitration reaction: dropwise adding 4ml of 65% concentrated nitric acid into the reaction solution containing 1-acetamido adamantane prepared in the step A under the conditions of ice-water bath and stirring, controlling the reaction temperature to be 0-10 ℃, reacting for 1.5 hours at normal temperature to obtain the reaction solution containing 3-nitro-1-acetamido adamantane,
step C, alkaline hydrolysis reaction: placing 80g of crushed ice into another four-neck flask, slowly adding the reaction solution containing 3-nitro-1-acetamido adamantane prepared in the step B into the crushed ice under the conditions of ice water bath and stirring, controlling the temperature of the system to be not more than 50 ℃, keeping the ice water bath condition, slowly adding potassium hydroxide solid, regulating the pH of the solution to be more than 12 to generate a large amount of white thick solid, keeping the ice water bath condition for reaction for 1 hour, removing the ice water bath, continuing the reaction for 1 hour, filtering to obtain filtrate and filter cake,
step D, purification: separating the filtrate obtained in the step C from the filter cake, regulating the pH of the filtrate to 7 by using hydrochloric acid, concentrating the filtrate to be powdery, adding 60ml of absolute ethyl alcohol, heating and refluxing for 1 hour at 65 ℃, transferring to an ice water bath, standing for 30min, carrying out suction filtration, and concentrating the filtrate to be powdery to obtain a solid A; directly using 60ml of absolute ethyl alcohol for heating and refluxing for 1 hour at 65 ℃, transferring to an ice water bath, standing for 30min, carrying out suction filtration, concentrating filtrate to obtain a powder form to obtain a solid B, combining the solid A and the solid B, using 10ml of acetone solution for heating and refluxing the powder, carrying out suction filtration, discarding the filtrate, and drying the filter cake to obtain 5.18g of 3-acetamido-1-adamantanol.
2. A process for preparing 3-acetamido-1-adamantanol, comprising the steps of:
step A, amidation reaction: pouring 40ml fuming sulfuric acid with the mass fraction of SO3 of 30% into a four-neck flask under the ice water bath condition, adding 8g adamantane under the stirring condition, slowly adding 8ml acetonitrile after the adamantane is completely dissolved, controlling the temperature of a reaction system to be not more than 20 ℃, transferring the system to normal temperature for reaction for 1 hour after the addition, obtaining a reaction solution containing 1-acetamido adamantane,
step B, nitration reaction: adding 15ml of fuming nitric acid into the reaction solution containing 1-acetamido adamantane prepared in the step A under the conditions of ice water bath and stirring, reacting for 1 hour under the ice water bath condition after the addition, then reacting for 1 hour at normal temperature to obtain the reaction solution containing 3-nitro-1-acetamido adamantane,
step C, alkaline hydrolysis reaction: placing 80g of crushed ice into another four-neck flask, transferring to an ice water bath, slowly adding the reaction solution containing 3-nitro-1-acetamido adamantane prepared in the step B into the crushed ice under the stirring condition, controlling the temperature of the system to be not more than 50 ℃, keeping the ice water bath condition, slowly adding sodium hydroxide solid, regulating the pH of the solution to be more than 12 to generate a large amount of white thick solid, keeping the ice water bath condition for reaction for 2 hours, removing the ice water bath, continuing the reaction for 2 hours, filtering to obtain filtrate and filter cake,
step D, purification: separating filtrate and filter cake, adjusting pH of filtrate to 10 with hydrochloric acid, concentrating filtrate to powder, adding 120ml of absolute ethanol, heating and refluxing at 75deg.C for 2 hr, transferring to ice water bath, standing for 30min, suction filtering, and concentrating filtrate to powder to obtain solid A; directly using 100ml of absolute ethyl alcohol for the filter cake, heating and refluxing for 2 hours at the temperature of 75 ℃, transferring to an ice water bath, standing for 30 minutes, carrying out suction filtration, and concentrating the filtrate to be powdery to obtain a solid B; the solid A and the solid B were combined, and the powder was heated under reflux using 20ml of a solution of acetone, suction-filtered, the filtrate was removed, and the cake was dried to give 9.98g of 3-acetamido-1-adamantanol.
3. A process for preparing 3-acetamido-1-adamantanol, comprising the steps of:
step A, amidation process: pouring 60ml fuming sulfuric acid with the mass fraction of SO3 of 20% into a four-neck flask under the ice water bath condition, adding 8g adamantane under the stirring condition, slowly adding 16ml acetonitrile after the adamantane is completely dissolved, controlling the temperature of a reaction system to be not more than 20 ℃, transferring the system to normal temperature for reaction for 1.5 hours after the addition, obtaining a reaction solution containing 1-acetamido adamantane,
step B, nitrifying: adding 10ml of fuming nitric acid into the reaction solution containing 1-acetamido adamantane prepared in the step A under the conditions of ice water bath and stirring, controlling the reaction temperature to be 0-10 ℃, reacting for 1.5 hours under the ice water bath condition, then reacting for 1.5 hours at normal temperature to obtain the reaction solution containing 3-nitro-1-acetamido adamantane,
step C, alkaline hydrolysis: placing 120g of crushed ice into another four-neck flask, transferring to an ice water bath, slowly adding the reaction solution containing 3-nitro-1-acetamido adamantane prepared in the step B into the crushed ice under the stirring condition, controlling the temperature of the system to be not more than 50 ℃, keeping the ice water bath condition, slowly adding sodium hydroxide solid, regulating the pH of the solution to be more than 12 to generate a large amount of white thick solid, keeping the ice water bath condition for reaction for 2 hours, removing the ice water bath, continuing to react for 1.5 hours, filtering to obtain filtrate and filter cake,
step D, purifying and separating filtrate and filter cake, regulating pH of the filtrate to 5 by using hydrochloric acid, concentrating the filtrate to be powdery, adding 100ml of absolute ethyl alcohol, heating and refluxing for 2 hours at 75 ℃, transferring to an ice water bath condition, standing for 30min, carrying out suction filtration, and concentrating the filtrate to be powdery to obtain a solid A; directly using 100ml of absolute ethyl alcohol for the filter cake, heating and refluxing for 2 hours at the temperature of 75 ℃, transferring to an ice water bath, standing for 30 minutes, carrying out suction filtration, and concentrating the filtrate to be powdery to obtain a solid B; the solid A and the solid B were combined together, and the powder was heated under reflux using 30ml of a solution of acetone, suction-filtered, the filtrate was removed, and the cake was dried to give 10.12g of 3-acetamido-1-adamantanol.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1574494A1 (en) * | 1997-01-14 | 2005-09-14 | Daicel Chemical Industries, Ltd. | Adamantane derivative |
| CN103965068A (en) * | 2013-01-25 | 2014-08-06 | 上海医药工业研究院 | 1-amide adamantane preparation method |
| CN105367470A (en) * | 2015-12-15 | 2016-03-02 | 天津民祥生物医药科技有限公司 | Method for preparing vildagliptin |
| CN108059601A (en) * | 2018-01-29 | 2018-05-22 | 重庆医科大学 | A kind of technique for preparing 3- amino-1-adamantane alcohols |
| WO2020163295A1 (en) * | 2019-02-04 | 2020-08-13 | Kansas State University Research Foundation | Chiral-substituted poly-n-vinylpyrrolidinones and complexes with bimetallic nanoclusters and uses thereof in asymmetric oxidation reactions |
-
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1574494A1 (en) * | 1997-01-14 | 2005-09-14 | Daicel Chemical Industries, Ltd. | Adamantane derivative |
| CN103965068A (en) * | 2013-01-25 | 2014-08-06 | 上海医药工业研究院 | 1-amide adamantane preparation method |
| CN105367470A (en) * | 2015-12-15 | 2016-03-02 | 天津民祥生物医药科技有限公司 | Method for preparing vildagliptin |
| CN108059601A (en) * | 2018-01-29 | 2018-05-22 | 重庆医科大学 | A kind of technique for preparing 3- amino-1-adamantane alcohols |
| WO2020163295A1 (en) * | 2019-02-04 | 2020-08-13 | Kansas State University Research Foundation | Chiral-substituted poly-n-vinylpyrrolidinones and complexes with bimetallic nanoclusters and uses thereof in asymmetric oxidation reactions |
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