CN112694410A - 3-amino-1-adamantanol and synthesis method thereof - Google Patents
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- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
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Abstract
The invention relates to the technical field of organic synthesis, in particular to 3-amino-1-adamantanol and a synthesis method thereof; the synthesis method of the 3-amino-1-adamantanol comprises the steps of mixing the 3-acetamido-1-adamantanol, strong base and an alcohol solvent, heating to 100 ℃ in a sealed manner, reacting for 5-10h, cooling, crystallizing, filtering, washing a filter cake by using the alcohol solvent, combining the filtrate, and distilling to remove the solvent to obtain the 3-amino-1-adamantanol. The synthesis method of 3-amino-1-adamantanol provided by the invention has the characteristics of simple and easy operation steps, high yield, high efficiency and suitability for industrial production; and the used raw material is adamantane, and special adamantane derivatives such as amantadine, adamantanecarboxylic acid and the like are not needed as raw materials, so that the production cost is further reduced.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to 3-amino-1-adamantanol and a synthesis method thereof.
Background
The incidence of diabetes has increased year by year and has become one of three chronic diseases threatening human health. The traditional oral medicine for treating diabetes mainly comprises the following components: sulfonylureas, biguanides, glinides, thiazolidinediones, a-glucosidase inhibitors, and the like. Dipeptidyl peptidase-IV (DPP-IV) inhibitors which are on the market in recent years are widely applied due to the advantages of definite hypoglycemic curative effect, low hypoglycemia risk, no obesity and the like.
Vildagliptin (Vildagliptin) is a highly selective dipeptidyl peptidase inhibitor developed by nova, approved by the european union in 2008, entering the china market in 2011, which has a global sales approaching $ thirteen billion in 2019. The 3-amino-1-adamantanol is an important intermediate for synthesizing vildagliptin, and has a molecular formula as follows: c10H17NO; molecular weight: 167.25 white crystals.
The current preparation methods of 3-amino-1-adamantanol include the following methods: (1) using amantadine hydrochloride as raw material, passing through H2SO4/HNO3Carrying out post-treatment such as system oxidation, alkaline hydrolysis, solvent extraction and the like to obtain 3-amino adamantanol; the process is uneconomical in raw materials. (2) The target product is synthesized by four steps of bromination, azidation, Curtius rearrangement, hydrolysis and the like by taking adamantane formic acid as a raw material, the synthesis method has more steps and low total yield, and the nitrine diphenyl phosphate is required to be used in the process, so the method has higher cost and is not suitable for industrial production. (3) Preparing 3-amino adamantanol by using amantadine as a raw material, molybdenum hexacarbonyl as a catalyst and carbon tetrabromide as an oxidant, wherein the yield is 80%; the catalyst used in the method is expensive and the cost is high. (4) Using amantadine hydrochloride as a raw material, and using trifluoro acetone peroxide as an oxidant to carry out selective oxidation to obtain a target product; the trifluoroperoxyacetone used in the method is unstable and difficult to obtain, and the reaction condition is difficult to industrialize.
Disclosure of Invention
Aiming at some problems in the prior art, the first aspect of the invention provides a method for synthesizing 3-amino-1-adamantanol, which comprises the steps of mixing 3-acetamido-1-adamantanol, strong base and an alcohol solvent, heating to 100 ℃ in a sealed manner, reacting for 5-10h, cooling, crystallizing, filtering, washing a filter cake by using the alcohol solvent, combining the filtrate, and distilling to remove the solvent to obtain the product.
In a preferred embodiment of the present invention, the alcohol solvent has 1 to 5 carbon atoms.
In a preferred embodiment of the present invention, the alcohol solvent is selected from one or more of isopropanol, ethanol, methanol, n-butanol, and isobutanol.
As a preferred technical solution of the present invention, the strong base is sodium hydroxide and/or potassium hydroxide.
As a preferable embodiment of the present invention, the method for preparing 3-acetamido-1-adamantanol comprises: mixing adamantane and strong acid, stirring at 30-100 ℃ for 0.5-3h, finishing dropwise adding a nitrile compound at the temperature of below 30 ℃ within 20-60min, continuously reacting at 40-60 ℃ for 1-10h to obtain a reaction solution, dropwise adding the reaction solution into the mixed extract liquor for extraction, separating the solution at the temperature of not more than 10 ℃, and extracting the aqueous phase with the extract liquor-1; and combining organic phases and distilling to obtain the product.
In a preferred embodiment of the present invention, the strong acid is selected from one or more of sulfuric acid, nitric acid, phosphoric acid, fuming sulfuric acid, and fuming nitric acid.
In a preferred embodiment of the present invention, the nitrile compound is an aliphatic nitrile.
As a preferable technical scheme of the invention, the aliphatic nitrile is acetonitrile and/or propionitrile.
As a preferable technical scheme of the invention, the mixed extraction liquid is a mixed liquid of alkali liquor and halogenated alkane.
The invention provides 3-amino-1-adamantanol prepared by the synthesis method of 3-amino-1-adamantanol.
Compared with the prior art, the invention has the following beneficial effects:
the synthesis method of 3-amino-1-adamantanol provided by the invention has the characteristics of simple and easy operation steps, high yield, high efficiency and suitability for industrial production; and the used raw material is adamantane, and special adamantane derivatives such as amantadine, adamantanecarboxylic acid and the like are not needed as raw materials, so that the production cost is further reduced.
Drawings
FIG. 1 shows 3-amino-1-adamantanol obtained in example 31HNMR picture
Detailed Description
The Strong base (Strong base) in the present invention means a substance in which all of the anions ionized in an aqueous solution are hydroxide ions. A strong base reacts with an acid to form a salt and water. The strong base and the weak base are relatively strong bases which are dissolved in water and can be completely ionized. The alkali and partial alkaline earth metal corresponding bases are generally strong bases. The pH of the solution is >12 in the standard case (concentration 0.1 mol/L).
The strong acid in the present invention is determined by the ionization constant in an aqueous solution, and a strong acid having a pKa (acidity coefficient, negative logarithm of ionization constant) of less than 1 (note: pKa 1-4 is a medium strong acid, and more than 4 is a weak acid.)
The present invention is illustrated by the following specific embodiments, but is not limited to the specific examples given below.
The first aspect of the invention provides a method for synthesizing 3-amino-1-adamantanol, which comprises the steps of mixing 3-acetamido-1-adamantanol, strong base and an alcohol solvent, heating to 100 ℃ in a sealed manner, reacting for 5-10h, cooling, crystallizing, filtering, washing a filter cake by using the alcohol solvent, combining filtrates, and distilling to remove the solvent to obtain the compound.
In one embodiment, the method for synthesizing 3-amino-1-adamantanol comprises the steps of mixing 3-acetamido-1-adamantanol, strong base, alcohol solvent and water, placing the mixture in an autoclave, fully replacing nitrogen, sealing, heating to 100 ℃ and 200 ℃, reacting for 5-10h, cooling, crystallizing, filtering, washing a filter cake by using the alcohol solvent, combining the filtrate, and distilling to remove the solvent to obtain the 3-amino-1-adamantanol.
In a preferred embodiment, the method for synthesizing 3-amino-1-adamantanol comprises mixing 3-acetamido-1-adamantanol, strong base, alcohol solvent and water, placing the mixture in an autoclave, fully replacing the nitrogen for three times, sealing and heating to 160 ℃, reacting for 6 hours, cooling and crystallizing, filtering, washing a filter cake with the alcohol solvent, combining the filtrate, and distilling to remove the solvent to obtain the 3-amino-1-adamantanol.
Preferably, the weight ratio of the 3-acetamido-1-adamantanol, the strong base, the alcoholic solvent and the water is 1.25: (0.5-5): (1-10): 1; more preferably, the weight ratio of the 3-acetamido-1-adamantanol, the strong base and the alcoholic solvent is 1.25: 0.7: 5: 1.
the weight ratio of the 3-acetamido-1-adamantanol, the strong base, the alcohol solvent and the water in the invention is 1.25: (0.5-5): (1-10): 1, in the synthesis process of the 3-amino-1-adamantanol, the raw materials can be in full contact reaction, so that the synthesis efficiency is improved, a certain yield is ensured, and the waste of the raw materials can be reduced.
Preferably, the strong base is sodium hydroxide and/or potassium hydroxide; more preferably, the strong base is sodium hydroxide.
The applicants have found that the yield of 3-amino-1-adamantanol obtained during the synthesis of 3-amino-1-adamantanol using sodium hydroxide in 3-acetamido-1-adamantanol is relatively high.
Preferably, the number of carbon atoms of the alcohol solvent is 1 to 5; further preferably, the alcohol solvent is selected from one or more of isopropanol, ethanol, methanol, n-butanol and isobutanol; more preferably, the alcoholic solvent is isopropanol.
The use of isopropanol in this application, to great with the solubility of alkali, effectively improved reaction efficiency and guaranteed the yield.
In one embodiment, the method of preparing 3-acetamido-1-adamantanol comprises: mixing adamantane and strong acid, stirring at 30-100 ℃ for 0.5-3h, finishing dropwise adding a nitrile compound at the temperature of below 30 ℃ within 20-60min, continuously reacting at 40-60 ℃ for 1-10h to obtain a reaction solution, dropwise adding the reaction solution into the mixed extract liquor for extraction, separating the solution at the temperature of not more than 10 ℃, and extracting the aqueous phase with the extract liquor-1; and combining organic phases and distilling to obtain the product.
Preferably, the nitrile compound is an aliphatic nitrile; further preferably, the aliphatic nitrile is acetonitrile and/or propionitrile; more preferably, the aliphatic nitrile is acetonitrile.
In a preferred embodiment, the method for preparing 3-acetamido-1-adamantanol comprises: mixing adamantane and strong acid, stirring at 30 ℃ for 0.5h, finishing dropwise adding a nitrile compound within 60min at the temperature of below 30 ℃, continuously reacting at 50 ℃ for 2h to obtain a reaction solution, dripping the reaction solution into a pre-cooled mixed extract for extraction, neutralizing, washing with water at the temperature of not more than 10 ℃, separating the solution, and extracting the water phase with an extract-1; and combining organic phases and distilling to obtain the product.
The applicant has surprisingly found that during the process for the preparation of 3-acetamido-1-adamantanol, the nitrile compounds are slowly added dropwise, the nitrile compound is dripped within 20-60min, particularly the nitrile compound is aliphatic nitrile, particularly, when the aliphatic nitrile is acetonitrile, the purity and the yield of the 3-acetamido-1-adamantanol can be obviously improved, further improving the yield of the 3-amino-1-adamantanol, the applicant believes that the possible reason is that the continuous dropping of the acetonitrile is ensured because the nitrile compound is dropped within 20-60min, in the reaction process, acetonitrile can be reacted at any time and sufficiently, if the adding speed is too fast, the acetonitrile is unstable in the system, the reaction is influenced, and the acetonitrile is possibly partially attenuated in the system for a long time. When the aromatic nitrile is used, the yield is low, and the aromatic nitrile may be nitrified in the system.
Preferably, the strong acid is selected from one or more of sulfuric acid, nitric acid, phosphoric acid, fuming sulfuric acid, fuming nitric acid; further preferably, the strong acid is sulfuric acid and nitric acid; further preferably, the mass ratio of the sulfuric acid to the nitric acid is (20-30): 1; more preferably, the mass ratio of sulfuric acid to nitric acid is 28: 1.
the concentration of sulfuric acid in the strong acid is 98%, and the concentration of nitric acid in the strong acid is 65%.
Preferably, the weight ratio of adamantane and strong acid is 1: (5-50); more preferably, the weight ratio of adamantane and strong acid is 1: 13.5.
in the invention, the weight ratio of the adamantane to the strong acid is 1: (5-50), on one hand, the original full utilization is realized, and on the other hand, the orderly reaction is ensured.
Preferably, the mixed extraction liquid is a mixed liquid of alkali liquor and halogenated alkane; further preferably, the weight ratio of the alkali liquor to the halogenated alkane is 1: (0.5-2); more preferably, the weight ratio of the alkali liquor to the halogenated alkane is 1: 1.
the solvent of the alkali liquor is water.
Preferably, the concentration of the alkali liquor is 1-10 wt%; more preferably, the lye concentration is 5 wt%.
The haloalkane and the alkali solution according to the present invention are not particularly limited and may be conventionally selected by those skilled in the art.
In a preferred embodiment, the haloalkane is dichloromethane.
The dichloromethane has higher extraction degree of 3-acetamido-1-adamantanol in the organic phase, and improves the yield of the 3-acetamido-1-adamantanol.
In a preferred embodiment, the lye is an aqueous solution of sodium hydroxide.
The aqueous solution of sodium hydroxide can effectively neutralize acid in the system, and does not influence the extraction of 3-acetamido-1-adamantanol by methylene chloride.
Preferably, extract-1 is dichloromethane.
The invention provides 3-amino-1-adamantanol prepared by the synthesis method of 3-amino-1-adamantanol.
Examples
Hereinafter, the present invention will be described in more detail by way of examples, but it should be understood that these examples are merely illustrative and not restrictive. The starting materials used in the examples which follow are all commercially available unless otherwise stated.
Example 1
The embodiment 1 of the invention provides a method for synthesizing 3-amino-1-adamantanol, which comprises the following specific steps: (1) mixing adamantane and strong acid, stirring at 30 ℃ for 3h, finishing dropwise adding a nitrile compound within 60min at the temperature of below 30 ℃, continuously reacting at 40 ℃ for 10h to obtain a reaction solution, dropwise adding the reaction solution into the mixed extract liquor for extraction, separating the solution under the condition that the temperature is not higher than 10 ℃, and extracting the water phase with extract liquor-1; combining organic phases, distilling to obtain 3-acetamido-1-adamantanol; (2) mixing 3-acetamido-1-adamantanol, strong base and alcohol solvent, sealing and heating to 160 ℃, reacting for 10 hours, cooling and crystallizing, filtering, washing a filter cake by using the alcohol solvent, combining the filtrate, and distilling to remove the solvent to obtain the compound preparation.
The weight ratio of the 3-acetamido-1-adamantanol to the strong base to the alcohol solvent is 1.25: 0.5: 1; the strong base is sodium hydroxide; the alcohol solvent is isopropanol; the nitrile compound is acetonitrile; the strong acid is sulfuric acid and nitric acid, and the mass ratio of the sulfuric acid to the nitric acid is 20: 1; the concentration of the sulfuric acid is 98 percent, and the concentration of the nitric acid is 65 percent; the weight ratio of the adamantane to the strong acid is 1: 5; the mixed extraction liquid is a mixed liquid of alkali liquor and halogenated alkane, and the weight ratio of the alkali liquor to the halogenated alkane is 1: 1; the concentration of the alkali liquor is 1 wt%; the alkane is dichloromethane; the alkali liquor is an aqueous solution of sodium hydroxide; extract-1 is dichloromethane.
Example 2
The embodiment 2 of the invention provides a method for synthesizing 3-amino-1-adamantanol, which comprises the following specific steps: (1) mixing adamantane and strong acid, stirring at 30 ℃ for 0.5h, finishing dropwise adding a nitrile compound within 60min at the temperature of below 30 ℃, continuously reacting at 60 ℃ for 1h to obtain a reaction liquid, dropwise adding the reaction liquid into the mixed extract liquid for extraction, separating liquid at the temperature of not more than 10 ℃, and extracting the water phase with the extract liquid-1; combining organic phases, distilling to obtain 3-acetamido-1-adamantanol; (2) mixing 3-acetamido-1-adamantanol, strong base and alcohol solvent, sealing, heating to 200 ℃, reacting for 5h, cooling, crystallizing, filtering, washing filter cake with alcohol solvent, combining filtrate, and distilling to remove solvent to obtain the final product.
The weight ratio of the 3-acetamido-1-adamantanol to the strong base to the alcohol solvent is 1.25: 5: 10; the strong base is sodium hydroxide; the alcohol solvent is isopropanol; the nitrile compound is acetonitrile; the strong acid is sulfuric acid and nitric acid, and the mass ratio of the sulfuric acid to the nitric acid is 30: 1; the concentration of the sulfuric acid is 98 percent, and the concentration of the nitric acid is 65 percent; the weight ratio of the adamantane to the strong acid is 1: 50; the mixed extraction liquid is a mixed liquid of alkali liquor and halogenated alkane, and the weight ratio of the alkali liquor to the halogenated alkane is 1: 1; the concentration of the alkali liquor is 10 wt%; the alkane is dichloromethane; the alkali liquor is an aqueous solution of sodium hydroxide; extract-1 is dichloromethane.
Example 3
Embodiment 3 of the present invention provides a method for synthesizing 3-amino-1-adamantanol, which comprises the following specific steps: (1) mixing adamantane and strong acid, stirring at 30 ℃ for 0.5h, finishing dropwise adding a nitrile compound within 60min at the temperature of below 30 ℃, continuously reacting at 50 ℃ for 2h to obtain a reaction solution, dripping the reaction solution into a pre-cooled mixed extract for extraction, neutralizing, washing with water at the temperature of not more than 10 ℃, separating the solution, and extracting the water phase with an extract-1; combining organic phases, distilling to obtain 3-acetamido-1-adamantanol; (2) mixing 3-acetamido-1-adamantanol, strong base, alcohol solvent and water, placing in a high-pressure kettle, fully replacing with nitrogen for three times, sealing, heating to 160 ℃, reacting for 6h, cooling, crystallizing, filtering, washing filter cake with alcohol solvent, combining filtrates, and distilling to remove solvent to obtain the final product.
The weight ratio of the 3-acetamido-1-adamantanol, the strong base, the alcohol solvent and the water is 1.25: 0.7: 5: 1; the strong base is sodium hydroxide; the alcohol solvent is isopropanol; the nitrile compound is acetonitrile; the strong acid is sulfuric acid and nitric acid, and the mass ratio of the sulfuric acid to the nitric acid is 28: 1; the concentration of the sulfuric acid is 98 percent, and the concentration of the nitric acid is 65 percent; the weight ratio of the adamantane to the strong acid is 1: 13.5; the mixed extraction liquid is a mixed liquid of alkali liquor and halogenated alkane, and the weight ratio of the alkali liquor to the halogenated alkane is 1: 1; the concentration of the alkali liquor is 5 wt%; the alkane is dichloromethane; the alkali liquor is an aqueous solution of sodium hydroxide; extract-1 is dichloromethane.
FIG. 1 shows the preparation of 3-amino-1-adamantanol obtained in example 3 of the present invention1HNMR map.
1HNMR, GC-MS and IR were characterized as follows:
1H NMR(400MHz,CDCl3)δ2.24(s,3H),1.64(s,5H),1.57(s,2H),1.51(s,7H)。
GC-MS(EI):m/z 167[M]+.
IR(KBr，cm-1)：3372，3329，3254，2923，2887，2846，1591，1354，1344，1307，1152，1103，1055，1043。
example 4
The embodiment 4 of the invention provides a method for synthesizing 3-amino-1-adamantanol, which is the same as the embodiment 3 in the specific implementation mode, and is different from the embodiment 3 in that the strong acid is sulfuric acid and fuming nitric acid, and the weight ratio of adamantane to the strong acid is 1: 13.5; the weight ratio of the sulfuric acid to the fuming nitric acid is 5: 1; the concentration of the sulfuric acid is 98%, and the concentration of the fuming nitric acid is 96%.
Example 5
The embodiment 5 of the invention provides a method for synthesizing 3-amino-1-adamantanol, which is the same as the embodiment 3 in the specific implementation mode, and is characterized in that the strong acid is phosphoric acid and nitric acid, and the weight ratio of adamantane to the strong acid is 1: 13.5; the weight ratio of the phosphoric acid to the nitric acid is 5: 1; the concentration of nitric acid was 65%.
Example 6
Example 6 of the present invention provides a process for the synthesis of 3-amino-1-adamantanol, the specific embodiment being the same as example 3 except that the strong acid is 20 wt% oleum.
Example 7
Embodiment 7 of the present invention provides a method for synthesizing 3-amino-1-adamantanol, which is similar to embodiment 3, except that the strong base is potassium hydroxide; the weight ratio of the 3-acetamido-1-adamantanol, the strong base, the alcohol solvent and the water is 1.25: 1: 5: 1.
example 8
Embodiment 8 of the present invention provides a method for synthesizing 3-amino-1-adamantanol, which is similar to embodiment 3, except that the alcohol solvent is ethanol.
Example 9
Embodiment 9 of the present invention provides a method for synthesizing 3-amino-1-adamantanol, which is the same as embodiment 3 except that the alcohol solvent is n-butanol.
Example 10
The embodiment 10 of the invention provides a method for synthesizing 3-amino-1-adamantanol, which comprises the following specific steps: (1) mixing adamantane and strong acid, stirring at 30 ℃ for 0.5h, finishing dropwise adding a nitrile compound within 10min at the temperature of below 30 ℃, continuously reacting at 50 ℃ for 2h to obtain a reaction solution, dripping the reaction solution into a pre-cooled mixed extract for extraction, neutralizing, washing with water at the temperature of not more than 10 ℃, separating the solution, and extracting the water phase with an extract-1; combining organic phases, distilling to obtain 3-acetamido-1-adamantanol; (2) mixing 3-acetamido-1-adamantanol, strong base, alcohol solvent and water, placing in a high-pressure kettle, fully replacing with nitrogen for three times, sealing, heating to 160 ℃, reacting for 6h, cooling, crystallizing, filtering, washing filter cake with alcohol solvent, combining filtrates, and distilling to remove solvent to obtain the final product.
The weight ratio of the 3-acetamido-1-adamantanol, the strong base, the alcohol solvent and the water is 1.25: 0.7: 5: 1; the strong base is sodium hydroxide; the alcohol solvent is isopropanol; the nitrile compound is acetonitrile; the strong acid is sulfuric acid and nitric acid, and the mass ratio of the sulfuric acid to the nitric acid is 28: 1; the concentration of the sulfuric acid is 98 percent, and the concentration of the nitric acid is 65 percent; the weight ratio of the adamantane to the strong acid is 1: 13.5; the mixed extraction liquid is a mixed liquid of alkali liquor and halogenated alkane, and the weight ratio of the alkali liquor to the halogenated alkane is 1: 1; the concentration of the alkali liquor is 5 wt%; the alkane is dichloromethane; the alkali liquor is an aqueous solution of sodium hydroxide; extract-1 is dichloromethane.
Example 11
Example 11 of the present invention provides a method for synthesizing 3-amino-1-adamantanol, which is similar to example 3, except that the nitrile compound is butyronitrile.
Performance evaluation
The initial total reaction raw materials, 3-acetamido-1-adamantanol and 3-amino-1-adamantanol were weighed respectively, and the yields were calculated. Wherein the yield (%) of 3-acetylamino-1-adamantanol is 100% moles of 3-acetylamino-1-adamantanol/moles of adamantane in the initial total reaction; yield (%) of 3-amino-1-adamantanol was 100% of the molar amount of 3-amino-1-adamantanol per the molar amount of 3-acetylamino-1-adamantanol charged.
TABLE 1
The foregoing examples are merely illustrative and serve to explain some of the features of the method of the present invention. The appended claims are intended to claim as broad a scope as is contemplated, and the examples presented herein are merely illustrative of selected implementations in accordance with all possible combinations of examples. Accordingly, it is applicants' intention that the appended claims are not to be limited by the choice of examples illustrating features of the invention. Also, where numerical ranges are used in the claims, subranges therein are included, and variations in these ranges are also to be construed as possible being covered by the appended claims.
Claims (10)
1. A synthesis method of 3-amino-1-adamantanol is characterized by comprising the steps of mixing 3-acetamido-1-adamantanol, strong base and an alcohol solvent, heating to 100 ℃ in a sealed manner, reacting for 5-10 hours, cooling, crystallizing, filtering, washing a filter cake by using the alcohol solvent, combining filtrates, and distilling to remove the solvent to obtain the 3-amino-1-adamantanol.
2. The method of synthesizing 3-amino-1-adamantanol according to claim 1, where in the alcohol solvent has 1 to 5 carbon atoms.
3. The method for synthesizing 3-amino-1-adamantanol according to claim 2, where in the alcoholic solvent is one or more selected from isopropanol, ethanol, methanol, n-butanol, and isobutanol.
4. The method of synthesizing 3-amino-1-adamantanol according to claim 1, where in the strong base is sodium hydroxide and/or potassium hydroxide.
5. The method for synthesizing 3-amino-1-adamantanol according to any one of claims 1 to 4, wherein the method for producing 3-acetamido-1-adamantanol comprises: mixing adamantane and strong acid, stirring at 30-100 ℃ for 0.5-3h, finishing dropwise adding a nitrile compound at the temperature of below 30 ℃ within 20-60min, continuously reacting at 40-60 ℃ for 1-10h to obtain a reaction solution, dropwise adding the reaction solution into the mixed extract liquor for extraction, separating the solution at the temperature of not more than 10 ℃, and extracting the aqueous phase with the extract liquor-1; and combining organic phases and distilling to obtain the product.
6. The method for synthesizing 3-amino-1-adamantanol according to claim 5, where in the strong acid is selected from one or more of sulfuric acid, nitric acid, phosphoric acid, fuming sulfuric acid, and fuming nitric acid.
7. The method of synthesizing 3-amino-1-adamantanol as claimed in claim 6 where in the nitrile compound is an aliphatic nitrile.
8. The method of synthesizing 3-amino-1-adamantanol of claim 7 where in the aliphatic nitrile is acetonitrile and/or propionitrile.
9. The method for synthesizing 3-amino-1-adamantanol according to claim 8, where in the mixed extract is a mixed solution of alkali solution and halogenated alkane.
10. 3-amino-1-adamantanol prepared by the method of synthesis of 3-amino-1-adamantanol according to any one of claims 1 to 9.
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| CN116924918A (en) * | 2023-07-20 | 2023-10-24 | 浙江荣耀生物科技股份有限公司 | Preparation method of 3-amino-1-adamantanol |
Citations (3)
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116924918A (en) * | 2023-07-20 | 2023-10-24 | 浙江荣耀生物科技股份有限公司 | Preparation method of 3-amino-1-adamantanol |
| CN116924918B (en) * | 2023-07-20 | 2024-02-09 | 浙江荣耀生物科技股份有限公司 | Preparation method of 3-amino-1-adamantanol |
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