阅读说明：本技术 氘代低碳胺的制备方法及制备装置 (Preparation method and preparation device of deuterated low-carbon amine ) 是由 陆雪根 李宏林 于 2021-09-13 设计创作，主要内容包括：本发明提供一种氘代低碳胺的制备方法及制备装置,其中,制备方法包括：步骤S1,提供氘代低碳胺的无机酸盐溶液；步骤S2,使所述氘代低碳胺的无机酸盐溶液与固体碱发生反应,得到所述氘代低碳胺。根据本发明实施例的制备方法,所获得的游离氘代低碳胺纯度高,且流程简单、生产效率高、通用性好,特别适合微量、半微量的游离氘代低碳胺的制备。(The invention provides a preparation method and a preparation device of deuterated low-carbon amine, wherein the preparation method comprises the following steps: step S1, providing inorganic acid salt solution of deuterated low-carbon amine; and step S2, reacting the inorganic acid salt solution of the deuterated low-carbon amine with solid alkali to obtain the deuterated low-carbon amine. According to the preparation method provided by the embodiment of the invention, the obtained free deuterated low-carbon amine has high purity, simple process, high production efficiency and good universality, and is particularly suitable for preparation of trace and semi-trace free deuterated low-carbon amine.)

1. A preparation method of deuterated low-carbon amine is characterized by comprising the following steps:

step S1, providing inorganic acid salt solution of deuterated low-carbon amine;

and step S2, reacting the inorganic acid salt solution of the deuterated low-carbon amine with solid alkali to obtain the deuterated low-carbon amine.

2. The method of claim 1, wherein the deuterated lower amine comprises methyl-d₃-amine, dimethyl-d₆Amine, N-methyl-d₃-amine, ethyl-d₅-amine, diethyl-d₁₀Amine, N-ethyl-d₅-any one or more of amines.

3. The method according to claim 1, wherein the inorganic acid salt solution of the deuterated low-carbon amine is an aqueous solution of a soluble hydrochloride, sulfate or nitrate of the deuterated low-carbon amine.

4. The method of claim 1, wherein the solid base is one or more of flake NaOH, flake KOH, granular NaOH, granular KOH, CaO particles.

5. The method of claim 1, further comprising:

and step S3, drying the deuterated low-carbon amine to obtain the dried deuterated low-carbon amine.

6. The method of manufacturing according to claim 5, further comprising:

and step S4, cooling and liquefying the dried deuterated low-carbon amine to obtain liquid deuterated low-carbon amine.

7. A device for preparing deuterated low-carbon amine is characterized by comprising:

a three-mouth bottle for containing solid alkali as one of the raw materials for reaction;

the constant-pressure dropping funnel is inserted into one bottleneck of the three-necked bottle and is used for dropping the inorganic acid salt solution of the deuterated low-carbon amine into the three-necked bottle;

the gas source conduit is inserted into the other bottle opening of the three-mouth bottle and is used for introducing carrier gas into the three-mouth bottle;

and one end of the first gas collecting pipe is inserted into the other bottle mouth of the three-mouth bottle and is used for collecting the deuterated low-carbon amine carried by the carrier gas.

8. The manufacturing apparatus according to claim 7, further comprising:

the gas dryer is used for containing a drying agent, and the other end of the first gas collecting pipe is inserted into the drying agent in the gas dryer;

one end of the second gas collecting pipe is communicated with the gas dryer so as to collect the dried deuterated low-carbon amine from the gas dryer.

9. The manufacturing apparatus according to claim 8, further comprising:

the other end of the second gas collecting pipe is inserted into one bottle mouth of the two-mouth collecting bottle;

the bottom end of the condenser is inserted into the other bottle mouth of the two-mouth collecting bottle and is communicated with the two-mouth collecting bottle, and the condenser further comprises a carrier gas outlet positioned above the condenser.

10. The manufacturing apparatus according to claim 9, further comprising:

and the two-port collecting bottle is arranged in the low-temperature bath, and a low-temperature refrigerant is contained in the low-temperature bath so as to further cool the deuterated low-carbon amine collected in the two-port collecting bottle.

Technical Field

The invention relates to the technical field of preparation of chemical drug intermediates, in particular to a preparation method and a preparation device of deuterated low-carbon amine.

Background

Deuterium (D) replaces some H atoms in a drug molecule, and the obtained deuterated drug can block related metabolic sites of the drug on the basis of not influencing the original biological activity of the drug, thereby reducing the generation of toxic metabolites, prolonging the half-life of the drug and reducing the single dose (Pirali T, Serafini M, Cargnin S, Genazzani A. applications of the drug in medical Chemistry [ J ]. Journal of medical Chemistry 2019,62(11): 5276-. The deuterated drugs have clear development targets, short period, high efficiency and low cost, and become one of the hot spots for developing new drugs (Dewitt S H, Maryanoff B E. Deutemled drug molecules: focus on FDA-improved deuterobetaine [ J ]. Biochemistry,2018,57(5): 472-.

The low carbon amine group is a common substituent group in a drug molecule and is also a key metabolic site in some drug molecules. The adoption of the deuterated low-carbon amine to replace the low-carbon amine group in the molecular structure of the original medicine is a feasible scheme for research and development of the deuterated medicine. The deuterated low-carbon amine is an important intermediate in the research and development process of deuterated drugs.

Substitution amination is an important method for introducing low-carbon amine groups into drug molecules. Free amine and amine salt can be used as displacement amination reagent, but the nucleophilic substitution activity difference between the free amine and the amine salt is large, and the using method is different. Free amine, in use, has high concentration, high activity, fast reaction speed, good product selectivity (Smith G, ZHao Y, Leytona J, Shanb B, Nguyena Q-de, Perumala M, Turtonc D,E,Luthrab S K,Robinsb E G,Aboagye E O.Radiosynthesis and pre-clinical evaluation of[¹⁸F]fluoro-[1,2-²H₄]choline[J]nuclear Medicine and Biology,2011,38, 39-51.); in use, the amine salt needs to be dissociated, so that the liquid phase concentration is low, the reaction speed is slow, and a large excess is needed to obtain higher yield (Costa B R de, Radesca L, Paolo L D, Bowen W D. Synthesis, chromatography, and Biological Evaluation of a Novel Class of N- (aryl 1) -N-alkyl-2- (1-pyrrolidino) amines: structural requirements and Binding Affinity at the sigma Receptor [ J].Journal of Medicinal Chemistry,1992,35:38-47.)。

In the displacement amination reaction, compared with amine salt, free amine has the obvious advantages of small dosage, fast reaction, high product selectivity and the like, and is a more suitable amination reagent.

However, the free deuterated low-carbon amine is gaseous at normal temperature and must be stored in a pressure tank for transportation and use. In use, the safety is low, and the quantification is difficult. In addition, the deuterated low-carbon amine compound is flammable gas, belongs to a controlled chemical, and has no supplier at home, thereby having great purchase difficulty.

At present, commercially available deuterated low-carbon amine compounds are usually inorganic acid salts such as hydrochloric acid or sulfuric acid, and are expensive, and if the compounds are directly used as amination reagents, the dosage is large, the conversion rate is low, the recovery is difficult, and the cost is high.

Therefore, a method for efficiently preparing free deuterated low-carbon amines is needed to promote the research and development of deuterated drugs containing deuterated low-carbon amine structures.

Disclosure of Invention

In view of the above, an object of the present invention is to provide a method for efficiently producing a free deuterated oligoamine.

It is another object of the present invention to provide a production apparatus capable of efficiently producing a free deuterated oligoamine.

In order to solve the technical problems, the invention adopts the following technical scheme:

the preparation method of the deuterated low-carbon amine according to the embodiment of the first aspect of the invention comprises the following steps:

step S1, providing inorganic acid salt solution of deuterated low-carbon amine;

and step S2, reacting the inorganic acid salt solution of the deuterated low-carbon amine with solid alkali to obtain the deuterated low-carbon amine.

Further, the deuterated low-carbon amine comprises methyl-d₃-amine, dimethyl-d₆Amine, N-methyl-d₃-amine, ethyl-d₅-amine, diethyl-d₁₀Amine, N-ethyl-d₅-any one or more of amines.

Further, the inorganic acid salt solution of the deuterated low-carbon amine is an aqueous solution of soluble hydrochloride, sulfate and nitrate of the deuterated low-carbon amine.

Further, the solid alkali is one or more of flake NaOH, flake KOH, granular NaOH, granular KOH and CaO particles.

Further, the preparation method also comprises the following steps:

and step S3, drying the deuterated low-carbon amine to obtain the dried deuterated low-carbon amine.

Further, the preparation method also comprises the following steps:

and step S4, cooling and liquefying the dried deuterated low-carbon amine to obtain liquid deuterated low-carbon amine.

A manufacturing apparatus according to an embodiment of a second aspect of the present invention includes:

a three-mouth bottle for containing solid alkali as one of the raw materials for reaction;

the constant-pressure dropping funnel is inserted into one bottleneck of the three-necked bottle and is used for dropping the inorganic acid salt solution of the deuterated low-carbon amine into the three-necked bottle;

the gas source conduit is inserted into the other bottle opening of the three-mouth bottle and is used for introducing carrier gas into the three-mouth bottle;

and one end of the first gas collecting pipe is inserted into the other bottle mouth of the three-mouth bottle and is used for collecting the deuterated low-carbon amine carried by the carrier gas.

Further, the preparation device further comprises:

the gas dryer is used for containing a drying agent, and the other end of the gas collecting pipe is inserted into the drying agent in the gas dryer;

one end of the second gas collecting pipe is communicated with the gas dryer so as to collect the dried deuterated low-carbon amine from the gas dryer.

Further, the preparation device further comprises:

the other end of the second gas collecting pipe is inserted into one bottle mouth of the two-mouth collecting bottle;

the bottom end of the condenser is inserted into the other bottle mouth of the two-mouth collecting bottle and is communicated with the two-mouth collecting bottle, and the condenser further comprises a carrier gas outlet positioned above the condenser.

Further, the preparation device further comprises:

and the two-port collecting bottle is arranged in the low-temperature bath, and a low-temperature refrigerant is contained in the low-temperature bath so as to further cool the deuterated low-carbon amine collected in the collecting bottle.

The technical scheme of the invention at least has one of the following beneficial effects:

according to the preparation method provided by the embodiment of the invention, the obtained free deuterated low-carbon amine has high purity, simple process, high production efficiency and good universality, and is particularly suitable for preparation of trace and semi-trace free deuterated low-carbon amine;

furthermore, by drying the generated free deuterated low-carbon amine, the moisture content of the dried deuterated low-carbon amine is low, and the dried deuterated low-carbon amine can be directly used for substitution amination reaction;

furthermore, the liquid deuterated low-carbon amine is obtained by cooling and liquefying the dried deuterated low-carbon amine, thereby being convenient for quantification and subsequent operation.

Drawings

Fig. 1 is a schematic diagram of a preparation apparatus of deuterated oligoamine according to an embodiment of the invention.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the drawings of the embodiments of the present invention. It is to be understood that the embodiments described are only a few embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the described embodiments of the invention, are within the scope of the invention.

Unless defined otherwise, technical or scientific terms used herein shall have the ordinary meaning as understood by one of ordinary skill in the art to which this invention belongs. The use of "first," "second," and similar terms in the present application do not denote any order, quantity, or importance, but rather the terms are used to distinguish one element from another. Also, the use of the terms "a" or "an" and the like do not denote a limitation of quantity, but rather denote the presence of at least one. The terms "connected" or "coupled" and the like are not restricted to physical or mechanical connections, but may include electrical connections, whether direct or indirect. "upper", "lower", "left", "right", and the like are used merely to indicate relative positional relationships, and when the absolute position of the object being described is changed, the relative positional relationships are changed accordingly.

First, a production apparatus of deuterated oligoamines according to an embodiment of the present invention will be described in detail with reference to the drawings.

As shown in fig. 1, the apparatus for preparing deuterated low-carbon amine according to the embodiment of the invention comprises: the device comprises a three-mouth bottle 1, a constant pressure dropping funnel 2, a gas source conduit 3 and a first gas collecting pipe 4.

Wherein, the three-mouth bottle 1 is used for containing solid alkali as one of reaction raw materials.

As specific examples of the solid base, for example, one or more of flake NaOH, flake KOH, granular NaOH, granular KOH, and CaO particles may be cited.

The constant pressure dropping funnel 2 is inserted into one bottle mouth of the three-mouth bottle 1 and is used for dropping the inorganic acid salt solution of the deuterated low-carbon amine into the three-mouth bottle 1.

As a specific example, the inorganic acid salt solution of the deuterated low-carbon amine may be, for example, an aqueous solution of a soluble hydrochloride, sulfate, or nitrate of the deuterated low-carbon amine.

The gas source conduit 3 is inserted into the other mouth of the three-mouth bottle and is used for introducing carrier gas into the three-mouth bottle 1.

The carrier gas is not involved in the reaction, but is used to carry the gas generated by the reaction for collection and introduction into the next step.

As an example, the carrier gas may be, for example: any one or more of N2 gas, Ar gas and air.

One end of a first gas collecting pipe 4 is inserted into the other mouth of the three-mouth bottle 1 and is used for collecting the deuterated low-carbon amine carried by the carrier gas.

In addition, in order to control the reaction temperature, the manufacturing apparatus may further include: a thermostat 10 on which the three-necked bottle 1 is placed to maintain the temperature of the system in the three-necked bottle 1 within a predetermined temperature range, for example, within a range of 0-100 ℃.

Further, the preparation apparatus according to the embodiment of the present invention may further include: a gas dryer 5 and a second gas collection tube 6.

The gas dryer 5 is used for containing a drying agent, and the other end of the first gas collecting pipe 4 is inserted into the drying agent in the gas dryer 5; one end of the second gas collecting pipe 2 is connected with a gas dryer 4 to collect the dried deuterated low-carbon amine from the gas dryer 4.

That is, the dissociated deuterated low carbon amine carried by the carrier gas from the reaction system is dried to reduce the moisture content therein, and the dried deuterated low carbon amine can be directly used for the substitution amination reaction due to the low moisture content.

The drying agent is not particularly limited as long as it can remove water and does not react with the deuterated low-carbon amine, and examples of the drying agent include flake-shaped NaOH, flake-shaped KOH, granular NaOH, granular KOH, CaO particles, and anhydrous CaCl₂Any one or more of the particles.

Still further, the manufacturing apparatus according to an embodiment of the present invention may further include: a two-port collection bottle 7 and a condenser 8. Specifically, the condenser 8 may use a dewar type condenser, for example.

The other end of the second gas collecting pipe 6 is inserted into one opening of the two-opening collecting bottle 7, and is inserted into the opening 71 on the left side as shown in fig. 1.

The bottom end 82 of the condenser 8 is inserted into the other bottle opening of the two-port collecting bottle 7, as shown in fig. 1, and is inserted into the bottle opening 72 of the two-port collecting bottle 7 located at the top end, and the condenser 8 is communicated with the two-port collecting bottle 7, that is, the condensation passage of the condenser is in gas-liquid communication with the two-port collecting bottle 7. Further, the condenser 8 includes a carrier gas outlet 81 located above.

That is, the carrier gas and the deuterated low carbon amine gas from the second gas collecting tube 6 flow into the collecting bottle through the mouth 71, and at this time, the carrier gas is in a gaseous state, and overflows into the condenser 8 from the top mouth 72 under the action of the carrier gas to exchange heat with the refrigerant, the deuterated low carbon amine is liquefied from a liquid state after the heat exchange, the liquid deuterated low carbon amine flows into the collecting bottle 7 from the bottom end 82 of the condenser 8 along the same trend, and the carrier gas in the deuterated low carbon amine does not reach the liquefaction temperature and overflows as a gas from the carrier gas outlet 81 located above the condenser 8.

Further, the condenser 8 may further include a coolant addition port (not shown).

Through the cooling and liquefaction, the liquid deuterated low-carbon amine is obtained, and the quantitative and subsequent operations are convenient.

As the coolant used in the condenser 8, for example, one or more of ice, dry ice-ethanol, liquid nitrogen, and dry ice-acetone may be used.

The deuterated low-carbon amine is cooled and liquefied into a liquid state by the action of the coolant of the condenser 8.

Further, in order to further maintain the deuterated low-carbon amine in a stable liquid state, the preparation device according to the embodiment of the invention may further include: and (4) low-temperature bath 9.

The two-mouth collecting bottle 7 is arranged in a low-temperature bath 9, and a low-temperature refrigerant is contained in the low-temperature bath 9 so as to further cool the deuterated low-carbon amine collected in the two-mouth collecting bottle.

As the low-temperature coolant in the low-temperature bath 9, for example, one or more of a brine bath, a dry ice-acetone bath, a liquid nitrogen-ethanol bath, and a liquid nitrogen-acetone bath may be used.

The following further describes a production method according to an embodiment of the present invention, with reference to the above production apparatus.

The preparation method of the deuterated low-carbon amine comprises the following steps:

step S1, providing inorganic acid salt solution of deuterated low-carbon amine;

and step S2, reacting the inorganic acid salt solution of the deuterated low-carbon amine with solid alkali to obtain the deuterated low-carbon amine.

Combining the above preparation apparatus, namely: and (3) dropwise adding the inorganic acid salt solution of the deuterated low-carbon amine into the three-necked bottle 1 through a constant-pressure dropping funnel 2, so that the inorganic acid salt solution of the deuterated low-carbon amine reacts with the solid base in the three-necked bottle 1 to obtain free deuterated low-carbon amine.

The preparation method can be used for preparing the following deuterated low-carbon amine: methyl-d₃-amine, dimethyl-d₆Amine, N-methyl-d₃-amine, ethyl-d₅-amine, diethyl-d₁₀Amine, N-ethyl-d₅-any one or more of amines.

The inorganic acid salt solution of the deuterated low-carbon amine added dropwise can be an aqueous solution of the soluble hydrochloride, sulfate or nitrate of the deuterated low-carbon amine.

The solid base in the three-necked flask 1 is, for example, one or more of flake NaOH, flake KOH, granular NaOH, granular KOH, CaO particles.

Further, the preparation method according to the embodiment of the invention further comprises the following steps:

and step S3, drying the deuterated low-carbon amine to obtain the dried deuterated low-carbon amine.

That is, the liberated deuterated oligoamine is dried.

Specifically, in order to rapidly introduce the dissociated deuterated low carbon amine into the drying process, a carrier gas is introduced into the three-necked flask 1 through the gas source conduit 3, the carrier gas carries the dissociated deuterated low carbon amine, the deuterated low carbon amine is introduced into the gas dryer 5 through the first gas collecting pipe 4, and the drying agent in the gas dryer 5 removes moisture in the deuterated low carbon amine.

Further, the preparation method according to the embodiment of the invention further comprises the following steps:

and step S4, cooling and liquefying the dried deuterated low-carbon amine to obtain liquid deuterated low-carbon amine.

Specifically, the deuterated low carbon amine dried by the gas dryer 5 is introduced into a condenser 8 through a second gas collecting pipe 6 and a two-port collecting bottle 7 to be cooled, is liquefied and then falls into the collecting bottle 7 to be collected, and is further cooled by a low-temperature refrigerant in a low-temperature bath 9, so that the stable and liquid deuterated low carbon amine is obtained.

According to the preparation method provided by the embodiment of the invention, the obtained free deuterated low-carbon amine has high purity, simple process, high production efficiency and good universality, and is particularly suitable for preparation of trace and semi-trace free deuterated low-carbon amine.

The following will further describe a method for preparing liquid deuterated oligoamines by using the preparation device of the invention with reference to specific examples.

Example 1:

2.0g of methyl-d are dissolved at room temperature using a constant pressure dropping funnel₃5mL deionized water solution of amine hydrochloride, dropped onto flake NaOH solid in 25mL three-necked flask, to produce large amount of methyl-d at once₃-amine gas.

In N₂Carried by a carrier gas, methyl-d₃Amine gas is passed through a gas drier filled with granular KOH desiccant, dewatered, introduced into a gas condensing unit, cooled and liquefied in a mini-dewar type condenser with dry ice as coolant, and dropped into a 10mL receiver placed in a dry ice-acetone bath for storage.

Weighing at low temperature and collecting liquid methyl-d₃Amine 0.78g, yield: 80.4 percent.

Example 2:

5.0g of methyl-d are dissolved at room temperature using a constant pressure dropping funnel₃15mL deionized water solution of amine sulfate dropped onto flaky KOH solid in a 50mL three-necked flask, producing a large amount of methyl-d at once₃-amine gas.

In N₂Carried by a carrier gas, methyl-d₃Amine gas is passed through a gas drier filled with granular KOH desiccant, after moisture is removed, it enters a gas condensing device, and is cooled and liquefied in a miniature Dewar type condenser using dry ice-ethanol as coolant, and then it is dropped into a 10mL collector placed in a liquid nitrogen-acetone bath for storage.

Weighing at low temperature and collecting liquid methyl-d₃Amine 1.90g, yield: 92.7 percent.

Example 3:

2.0g of dimethyl-d is dissolved at 50 ℃ by using a constant pressure dropping funnel₆5 of amine hydrochloridemL deionized water solution is dripped into a CaO solid in a 25mL three-neck flask to generate a large amount of dimethyl-d₆-amine gas.

Dimethyl-d carried in Ar carrier gas₆Amine gas is dehydrated by a gas drier filled with a block CaO desiccant, enters a gas condensing device, is cooled and liquefied in a miniature Dewar type condenser taking dry ice-acetone as a coolant, and is dropped into a 10mL collector placed in a liquid nitrogen-ethanol bath for storage.

Weighing at low temperature and collecting liquid dimethyl-d₆Amine 0.98g, yield: 83.6 percent.

Example 4:

at 70 deg.C, 5.0g dimethyl-d will be dissolved by using a constant pressure dropping funnel₆15mL deionized water solution of amine sulfate dropped onto CaO solid in a 50mL three-necked flask to produce a large amount of dimethyl-d at once₆-amine gas.

Dimethyl-d carried in Ar carrier gas₆Amine gas by charging with CaCl in bulk₂And (3) after moisture is removed by a gas drier of the drying agent, the gas drier enters a gas condensing device, is cooled and liquefied in a miniature Dewar type condenser taking dry ice-acetone as a cooling agent, and is dripped into a 10mL collector placed in a liquid nitrogen-ethanol bath for storage.

Weighing at low temperature and collecting liquid dimethyl-d₆Amine 2.30g, yield: 90.2 percent.

Example 5:

at room temperature, 2.0g of N-methyl-d is dissolved by using a constant pressure dropping funnel₃5mL deionized water solution of amine hydrochloride dropped onto granular KOH solid in a 25mL three-necked flask, producing large amounts of N-methyl-d at once₃-amine gas.

Carried by an air carrier gas, N-methyl-d₃Amine gas is dehydrated by a gas drier filled with a bulk CaO desiccant, enters a gas condensing device, is cooled and liquefied in a miniature Dewar type condenser taking dry ice-acetone as a coolant, and is dropped into a 10mL collector placed in a liquid nitrogen bath for storage.

Low temperatureWeighing, and collecting solid N-methyl-d₃Amine 1.02g, yield: 89.3 percent.

Example 6:

at room temperature, 2.0g of ethyl-d was dissolved using a constant pressure dropping funnel₅5mL deionized water solution of amine hydrochloride dropped onto granular KOH solid in a 25mL three-necked flask to produce large amounts of ethyl-d at once₅-amine gas.

In N₂Carried by a carrier gas, ethyl-d₅Amine gas is dehydrated by a gas drier filled with flake NaOH desiccant, enters a gas condensing device, is cooled and liquefied in a miniature Dewar type condenser with dry ice as a coolant, and is dropped into a 10mL collector placed in a dry ice-acetone bath for storage.

Weighing at low temperature and collecting ethyl-d₅Amine 0.96g, yield: 82.6 percent.

Example 7:

2.0g of diethyl-d was dissolved at 80 ℃ using a constant pressure dropping funnel₁₀5mL deionized water solution of amine hydrochloride dropped onto CaO solid in a 25mL three-necked flask, producing a large amount of diethyl-d at once₁₀-amine gas.

Carried by Ar carrier gas, diethyl-d₁₀Amine gas is passed through a gas drier filled with a cake-shaped CaO desiccant, after moisture is removed, it enters a gas condensing unit, is cooled and liquefied in a miniature Dewar type condenser with ice as a coolant, and is dropped into a 10mL collector placed in a dry ice-acetone bath for storage.

Weighing at low temperature and collecting liquid diethyl-d₁₀Amine 0.98g, yield: 70.0 percent.

Example 8:

2.0g of N-ethyl-d is dissolved at 60 ℃ by using a constant pressure dropping funnel₅5mL deionized water solution of amine hydrochloride dropped onto CaO solid in a 25mL three-necked flask to produce a large amount of N-ethyl-d at once₅-amine gas.

Carried by Ar carrier gas, N-ethyl-d₅Passing amine gas through a packed CaO desiccant cakeAnd the gas drier is used for removing water, then enters a gas condensing device, is cooled and liquefied in a miniature Dewar type condenser with ice blocks as a coolant, and is dripped into a 10mL collector placed in an ice salt water bath for storage.

Weighing at low temperature, collecting liquid N-ethyl-d₅Amine 1.10g, yield: 80.4 percent.

While the foregoing is directed to the preferred embodiment of the present invention, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention as defined in the appended claims.