阅读说明：本技术 一种2-(噁唑基)乙胺的制备方法 (A kind of preparation method of 2- (oxazolyl) ethamine ) 是由 蒋德宏 杨雄 代瑞阳 武军晨 白峰 于 2019-09-16 设计创作，主要内容包括：本发明公开了一种2-(噁唑基)乙胺的制备方法；本发明2-(噁唑基)乙胺的制备方法,有效避免噁唑开环副反应,重复性好,转化率和收率高,易纯化；反应条件温和,安全性高,降低对操作人员的安全隐患,降低了生产的操作安全等级,绿色环保；得到的2-(噁唑基)乙胺产品纯度高,质量好,有利于实现工业化。(The invention discloses a kind of preparation methods of 2- (oxazolyl) ethamine；The preparation method of 2- (oxazolyl) ethamine of the present invention, effectively avoids oxazole open loop side reaction, reproducible, conversion ratio and high income, easy purification；Reaction condition is mild, highly-safe, reduces the security risk to operator, reduces the safe operation grade of production, environmentally protective；Obtained 2- (oxazolyl) ethamine product purity is high, high-quality, is advantageously implemented industrialization.)

1. a kind of preparation method of 2- (oxazolyl) ethamine, which is characterized in that the preparation method includes following preparation method road Line and step:

2- (oxazolyl) ethamine is as shown in formula A:

Preparation method route is as follows:

Compound A-1 is carried out reduction reaction by step 1 in the presence of reducing agent and alcoholic solvent, and post-processing obtains compound A-2；

Step 2 reacts compound A-2 in the presence of methylsufonyl chloride, organic base and organic solvent, and post-processing obtains Compound A-3；

Step 3 carries out compound A-3 anti-in the presence of trimethylsilyl cyanide, inorganic base, catalyst and non-protonic solvent It answers, post-processing obtains compound A-4；

Compound A-4 is carried out hydrogenation reduction by step 4 in the presence of reducing agent and alcoholic solvent, and post-processing obtains commercialization Close object 2- (oxazolyl) ethylamine compounds A.

2. method as described in claim 1, which is characterized in that in the step 1,

The reducing agent is lithium borohydride, sodium borohydride, tetra lithium aluminium hydride, one or more in diisobutyl aluminium hydride；

The alcoholic solvent is methanol, ethyl alcohol, propyl alcohol, isopropanol, butanol, isobutanol, one or more in the tert-butyl alcohol；

The weight ratio of the A-1 and reducing agent is 3:1~4:1；

The w/v of the A-1 and alcoholic solvent is 1:30~1:40.

3. method as described in claim 1, which is characterized in that in the step 2,

The organic base is triethylamine, DIPEA, DBU, DBN, DMAP, pyridine, N-methylmorpholine, tetramethylethylenediamine, the tert-butyl alcohol It is potassium, sodium tert-butoxide, sodium methoxide, one or more in sodium ethoxide；

The organic solvent is methylene chloride, chloroform, 1,2- dichloroethanes, one or more in carbon tetrachloride；

The weight ratio of the A-2 and methylsufonyl chloride is 1:2~1:3；

The weight ratio of the A-2 and organic base is 1:1.2~1:2；

The w/v of the A-2 and organic solvent is 1:30~1:60.

4. method as described in claim 1, which is characterized in that in the step 3,

The inorganic base is potassium carbonate, cesium carbonate, sodium hydroxide, one or more in sodium carbonate；

The non-protonic solvent is acetonitrile, one or more in DMF, DMA, DMSO；

The catalyst is tetrabutyl ammonium fluoride, tetrabutylammonium bromide, one or more in tetrabutylammonium chloride；

The weight ratio of the A-3 and trimethylsilyl cyanide is 1.2:1~1.5:1；

The weight ratio of the A-3 and inorganic base is 1:1~1:2；

The weight ratio of the A-3 and catalyst is 1:2~1:3；

The w/v of the A-3 and non-protonic solvent is 1:20~1:30.

5. method as described in claim 1, which is characterized in that in the step 4,

The reducing agent is Raney's nickel, palladium charcoal, one or more in palladium dydroxide；

The alcoholic solvent is methanol, ethyl alcohol, propyl alcohol, isopropanol, butanol, isobutanol, one or more in the tert-butyl alcohol；

The weight ratio of the A-4 and reducing agent is 2:1~3:1；

The w/v of the A-4 and alcoholic solvent is 1:80~1:90.

6. the method as described in claim 1, which is characterized in that

In the step 1,

The weight ratio of A-1 and reducing agent is 3.2:1~3.5:1；

The w/v of A-1 and alcoholic solvent is 1:35~1:40；

In the step 2,

The weight ratio of A-2 and organic base is 1:1.2~1:1.5；

The w/v of A-2 and organic solvent is 1:50~1:60.

7. the method as described in claim 1, which is characterized in that

In the step 3,

The weight ratio of A-3 and inorganic base is 1:1.1~1:1.5；

The weight ratio of A-3 and catalyst is 1:2~1:2.3；

The w/v of A-3 and non-protonic solvent is 1:25~1:30；

In the step 4

The weight ratio of A-4 and reducing agent is 2.5:1~3:1；

The w/v of A-4 and alcoholic solvent is 1:85~1:90.

8. the method as described in claim 1, which is characterized in that the preparation method of 2- (oxazolyl) ethamine is specially 2- The preparation method of (2- oxazolyl) ethamine, including following preparation method route and step:

2- (2- oxazolyl) ethamine is as shown in formula A-a:

Preparation method route is as follows:

Compound A-1a is carried out reduction reaction by step 1 in the presence of reducing agent and alcoholic solvent, and post-processing obtains compound A- 2a；

Step 2 reacts compound A-2a in the presence of methylsufonyl chloride, organic base and organic solvent, post-processes To compound A-3a；

Step 3 carries out compound A-3a in the presence of trimethylsilyl cyanide, inorganic base, catalyst and non-protonic solvent Reaction, post-processing obtain compound A-4a；

Compound A-4a is carried out hydrogenation reduction by step 4 in the presence of reducing agent and alcoholic solvent, and post-processing obtains commercialization Close object 2- (2- oxazolyl) ethylamine compounds A-a.

9. method as described in claim 1, which is characterized in that the preparation method of 2- (oxazolyl) ethamine is specially 2- (4- Oxazolyl) ethamine preparation method, including following preparation method route and step:

2- (4- oxazolyl) ethamine is as shown in formula A-b:

Preparation method route is as follows:

Compound A-1b is carried out reduction reaction by step 1 in the presence of reducing agent and alcoholic solvent, and post-processing obtains compound A- 2b；

Step 2 reacts compound A-2b in the presence of methylsufonyl chloride, organic base and organic solvent, post-processes To compound A-3b；

Step 3 carries out compound A-3b in the presence of trimethylsilyl cyanide, inorganic base, catalyst and non-protonic solvent Reaction, post-processing obtain compound A-4b；

Compound A-4b is carried out hydrogenation reduction by step 4 in the presence of reducing agent and alcoholic solvent, and post-processing obtains commercialization Close object 2- (4- oxazolyl) ethylamine compounds A-b.

10. 2- (oxazolyl) ethamine that a kind of any one of claim 1~9 the method obtains, which is characterized in that the 2- (oxazolyl) ethamine product purity is greater than 95%.

Technical field

The present invention relates to technical field of organic synthesis more particularly to a kind of preparation methods of 2- (oxazolyl) ethamine.

Background technique

2- (oxazolyl) ethylamine compounds contain amino active site, are that commonly synthesis is built in a variety of lead compounds Block.2- (2- oxazolyl) ethamine is leukotriene A4 hydrolase inhibitor, the relevant TRPA1 receptor antagonist of respiratory disease Agent, HIV and FIV infect inhibitors of chemokine receptors, treat and prevent the guideizations such as disease activity substance caused by RNA virus Close indispensable building block when object preparation synthesis；2- (4- oxazolyl) ethamine is histamine H2-receptor agonist, also The relevant TRPA1 receptor antagonist of respiratory disease treats and prevents the guideizations such as disease activity substance caused by RNA virus Close building block when object preparation synthesis.There is great potential in medical research field.

The existing disclosed preparation method of 2- (oxazolyl) ethylamine compounds includes by protecting by raw material and nitrogen of oxazole Halogenated ethamine substitution reaction occurs in the presence of lithium reagent, then deprotection obtains 2- (oxazolyl) ethylamine compounds.

For example, particular compound 2- (2- oxazolyl) ethamine (CAS in 2- (oxazolyl) ethylamine compounds No.885628-79-1) existing disclosed preparation method route is as follows:

In this preparation method, under conditions of the lithium reagents such as highly basic n-BuLi open loop easily occurs for the oxazole as raw material, How complicated side reaction is, keeps repeatability in practical preparation manipulation poor, or even make to be difficult to obtain target product in practical preparation, purifies Difficulty, that product purity is low is of poor quality for 2- (2- oxazolyl) ethamine；Also, lithium reagent is hazardous agents, uses dosage as reagent Big risk is high, is unfavorable for environmental protection and sustainable development, is unfavorable for amplification industrialization.

Particular compound 2- (4- oxazolyl) ethamine (CAS No.227475- in 2- (oxazolyl) ethylamine compounds 42-5), target compound cannot get using above-mentioned similar preparation method completely, and so far there are no pertinent literature reports other Preparation synthetic method.

Industrial amplification production is not able to satisfy in view of many defects and existing preparation method of above-mentioned existing preparation method The quality requirement of 2- (oxazolyl) ethylamine compounds product.Therefore, to the preparation method of exploitation 2- (oxazolyl) ethamine, improve There is an urgent need for the defects of existing preparation method.

Summary of the invention

In view of the above drawbacks of the prior art, the technical problem to be solved by the present invention is to existing 2- (oxazolyl) ethamine The preparation method of class compound, Yi Fasheng open loop, how complicated side reaction is, and repeatable poor, purification difficult uses lithium reagent danger Chemicals, danger coefficient is high, dangerous, is unfavorable for industrializing.

To achieve the above object, the present invention provides a kind of preparation method of 2- (oxazolyl) ethamine (formula A),

The preparation method comprises the following steps:

Compound A-1 is carried out reduction reaction by step 1 in the presence of reducing agent and alcoholic solvent, and post-processing obtains compound A-2；

Step 2 reacts compound A-2 in the presence of methylsufonyl chloride, organic base and organic solvent, post-processing Obtain compound A-3；

Step 3, by compound A-3 in the presence of trimethylsilyl cyanide, inorganic base, catalyst and non-protonic solvent into Row reaction, post-processing obtain compound A-4；

Compound A-4 is carried out hydrogenation reduction by step 4 in the presence of reducing agent and alcoholic solvent, and post-processing is produced Product compound 2- (oxazolyl) ethamine (formula A).

Preparation method route is as follows:

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 1, the reducing agent are lithium borohydride, boron It is sodium hydride, tetra lithium aluminium hydride, one or more in diisobutyl aluminium hydride；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 1, the alcoholic solvent are methanol, ethyl alcohol, third It is alcohol, isopropanol, butanol, isobutanol, one or more in the tert-butyl alcohol；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 1, the weight ratio of the A-1 and reducing agent (gram: gram) it is 3:1~4:1；

Further, in the step 1, the weight ratio of A-1 and reducing agent (gram: gram) it is 3.2:1~3.5:1；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 1, the weighing body of the A-1 and alcoholic solvent Product is 1:30~1:40 than (gram: milliliter)；

Further, in the step 1, and the w/v of A-1 and alcoholic solvent (gram: milliliter) it is 1:35~1:40；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 2, the organic base be triethylamine, DIPEA, DBU, DBN, DMAP, pyridine, N-methylmorpholine, tetramethylethylenediamine, potassium tert-butoxide, sodium tert-butoxide, sodium methoxide, ethyl alcohol It is one or more in sodium；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 2, the organic solvent be methylene chloride, It is chloroform, 1,2- dichloroethanes, one or more in carbon tetrachloride；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 2, the weight of the A-2 and methylsufonyl chloride Amount is 1:2~1:3 than (gram: gram)；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 2, the weight ratio of the A-2 and organic base (gram: gram) it is 1:1.2~1:2；

Further, in the step 2, the weight ratio of A-2 and organic base (gram: gram) it is 1:1.2~1:1.5；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 2, the weight of the A-2 and organic solvent Volume ratio (gram: milliliter) it is 1:30~1:60；

Further, in the step 2, and the w/v of A-2 and organic solvent (gram: milliliter) it is 1:50~1:60；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 3, the inorganic base are potassium carbonate, carbonic acid It is caesium, sodium hydroxide, one or more in sodium carbonate；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 3, the non-protonic solvent be acetonitrile, It is one or more in DMF, DMA, DMSO；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 3, the catalyst are tetrabutyl fluorination It is ammonium, tetrabutylammonium bromide, one or more in tetrabutylammonium chloride；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 3, the A-3 and trimethylsilyl cyanide Weight ratio (gram: gram) it is 1.2:1~1.5:1；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 3, the weight ratio of the A-3 and inorganic base (gram: gram) it is 1:1~1:2；

Further, in the step 3, the weight ratio of A-3 and inorganic base (gram: gram) it is 1:1.1~1:1.5；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 3, the weight ratio of the A-3 and catalyst (gram: gram) it is 1:2~1:3；

Further, in the step 3, the weight ratio of A-3 and catalyst (gram: gram) it is 1:2~1:2.3；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 3, the A-3 and non-protonic solvent W/v (gram: milliliter) it is 1:20~1:30；

Further, in the step 3, the w/v of A-3 and non-protonic solvent (gram: milliliter) be 1:25~1: 30；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 4, the reducing agent be Raney's nickel, palladium charcoal, It is one or more in palladium dydroxide；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 4, the alcoholic solvent are methanol, ethyl alcohol, third It is alcohol, isopropanol, butanol, isobutanol, one or more in the tert-butyl alcohol；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 4, the weight ratio of the A-4 and reducing agent (gram: gram) it is 2:1~3:1；

Further, in the step 4, the weight ratio of A-4 and reducing agent (gram: gram) it is 2.5:1~3:1；

The preparation method of 2- (oxazolyl) ethamine according to the present invention, in step 4, the weighing body of the A-4 and alcoholic solvent Product is 1:80~1:90 than (gram: milliliter)；

Further, in the step 4, and the w/v of A-4 and alcoholic solvent (gram: milliliter) it is 1:85~1:90；

Certain preferred embodiments according to the present invention, the preparation method of 2- (oxazolyl) ethamine, step 1 embodiment party Formula is as follows: compound A-1 and lithium borohydride in an inert atmosphere, using alcoholic solvent as reaction dissolvent, are stirred at room temperature anti- It answers 2~3 hours, reaction solution post-processes to obtain target compound A-2；Wherein, A-1 and lithium borohydride feed intake weight ratio (gram: Gram) it is 3.2:1~3.5:1；The w/v (gram: milliliter) of A-1 and alcoholic solvent is 1:35~1:40；

Certain preferred embodiments according to the present invention, the preparation method of 2- (oxazolyl) ethamine, step 2 embodiment party Formula is as follows: compound A-2, triethylamine being added in dichloromethane solvent, methylsufonyl chloride is added, stirs in an inert atmosphere Mix reaction 2~3 hours, post-processing obtains compound A-3；Wherein, the weight ratio (gram: gram) of A-2 and methylsufonyl chloride be 1:2~ 1:3；The weight ratio (gram: gram) of A-2 and triethylamine is 1:1.2~1:1.5；A-2 and methylene chloride w/v (gram: milli Rise) it is 1:50~1:60；

Certain preferred embodiments according to the present invention, the preparation method of 2- (oxazolyl) ethamine, step 3 embodiment party Formula is as follows: compound A-3, trimethylsilyl cyanide, potassium carbonate, tetrabutyl ammonium fluoride are dissolved in acetonitrile, in an inert atmosphere It is stirred to react 2~3 hours, post-processing obtains compound A-4；Wherein, the weight ratio (gram: gram) of A-3 and trimethylsilyl cyanide is 1.2:1~1.5:1；The weight ratio (gram: gram) of A-3 and potassium carbonate is 1:1.1~1:1.5；The weight of A-3 and tetrabutyl ammonium fluoride Than (gram: gram) it is 1:2~1:2.3；The w/v (gram: milliliter) of A-3 and acetonitrile is 1:25~1:30；

Certain preferred embodiments according to the present invention, the preparation method of 2- (oxazolyl) ethamine, step 4 embodiment party Formula is as follows: by compound A-4, Raney's nickel and alcoholic solvent feed intake under autoclave, hydrogen environment pressurize room temperature be stirred to react 8 ~18 hours, post-processing obtained product compound 2- (oxazolyl) ethamine (formula A)；Wherein, A-4 and Raney's nickel weight ratio (gram: Gram) it is 2.5:1~3:1；The w/v (gram: milliliter) of A-4 and alcoholic solvent is 1:85~1:90；

In better embodiment of the invention, in the step 1, the weight ratio of the A-1 and reducing agent (gram: gram) be 3.2:1；

In another better embodiment of the invention, in the step 1, the weight ratio of the A-1 and reducing agent (gram: Gram) it is 4:1；

In another better embodiment of the invention, in the step 1, the weight ratio of the A-1 and reducing agent (gram: Gram) it is 3.5:1；

In better embodiment of the invention, in the step 1, the w/v of the A-1 and alcoholic solvent (gram: milli Rise) it is 1:30；

In another better embodiment of the invention, the w/v of the A-1 and alcoholic solvent (gram: milliliter) be 1: 40；

In another better embodiment of the invention, the w/v of the A-1 and alcoholic solvent (gram: milliliter) be 1: 35；

In better embodiment of the invention, in the step 2, the weight ratio of the A-2 and methylsufonyl chloride (gram: gram) For 1:2；

In another better embodiment of the invention, in the step 2, the weight ratio of the A-2 and methylsufonyl chloride (gram: gram) it is 1:3；

In another better embodiment of the invention, in the step 2, the weight ratio of the A-2 and methylsufonyl chloride (gram: gram) it is 1:2.5；

In better embodiment of the invention, in the step 2, the weight ratio of the A-2 and organic base (gram: gram) it is 1: 1.2；

In another better embodiment of the invention, in the step 2, the weight ratio of the A-2 and organic base (gram: Gram) it is 1:2；

In another better embodiment of the invention, in the step 2, the weight ratio of the A-2 and organic base (gram: Gram) it is 1:1.4；

In better embodiment of the invention, in the step 2, the w/v of the A-2 and organic solvent (gram: Milliliter) it is 1:30；

In another better embodiment of the invention, in the step 2, the bulking value of the A-2 and organic solvent Than (gram: milliliter) it is 1:60；

In another better embodiment of the invention, in the step 2, the bulking value of the A-2 and organic solvent Than (gram: milliliter) it is 1:50；

In better embodiment of the invention, in the step 3, the weight ratio of the A-3 and trimethylsilyl cyanide (gram: gram) it is 1.2:1；

In another better embodiment of the invention, in the step 3, the weight of the A-3 and trimethylsilyl cyanide Than (gram: gram) it is 1.5:1；

In another better embodiment of the invention, in the step 3, the weight of the A-3 and trimethylsilyl cyanide Than (gram: gram) it is 1.3:1；

In better embodiment of the invention, in the step 3, the weight ratio of the A-3 and inorganic base (gram: gram) be 1:1.1；

In another better embodiment of the invention, in the step 3, the weight ratio of the A-3 and inorganic base (gram: Gram) it is 1:2；

In another better embodiment of the invention, in the step 3, the weight ratio of the A-3 and inorganic base (gram: Gram) it is 1:1.5；

In better embodiment of the invention, in the step 3, the weight ratio of the A-3 and catalyst (gram: gram) be 1:2.2；

In another better embodiment of the invention, in the step 3, the weight ratio of the A-3 and catalyst (gram: Gram) it is 1:3；

In another better embodiment of the invention, in the step 3, the weight ratio of the A-3 and catalyst (gram: Gram) it is 1:2.3；

In better embodiment of the invention, in the step 3, the bulking value of the A-3 and non-protonic solvent Than (gram: milliliter) it is 1:25；

In another better embodiment of the invention, in the step 3, the weight of the A-3 and non-protonic solvent Volume ratio (gram: milliliter) it is 1:30；

In another better embodiment of the invention, in the step 3, the weight of the A-3 and non-protonic solvent Volume ratio (gram: milliliter) it is 1:28；

In better embodiment of the invention, in the step 4, the weight ratio of the A-4 and reducing agent (gram: gram) be 2:1；

In another better embodiment of the invention, in the step 4, the weight ratio of the A-4 and reducing agent (gram: Gram) it is 3:1；

In another better embodiment of the invention, in the step 4, the weight ratio of the A-4 and reducing agent (gram: Gram) it is 2.5:1；

In better embodiment of the invention, in the step 4, the w/v of the A-4 and alcoholic solvent (gram: Milliliter) it is 1:89；

In another better embodiment of the invention, in the step 4, the w/v of the A-4 and alcoholic solvent (gram: milliliter) it is 1:80；

In another better embodiment of the invention, in the step 4, the w/v of the A-4 and alcoholic solvent (gram: milliliter) it is 1:85；

In better embodiment of the invention, the preparation method of 2- (oxazolyl) ethamine is specially 2- (2- oxazole Base) ethamine (formula A-a) preparation method,

Specifically includes the following steps:

Compound A-1a is carried out reduction reaction by step 1 in the presence of reducing agent and alcoholic solvent, and post-processing obtains compound A-2a；

Step 2 reacts compound A-2a in the presence of methylsufonyl chloride, organic base and organic solvent, rear to locate Reason obtains compound A-3a；

Step 3, by compound A-3a in the presence of trimethylsilyl cyanide, inorganic base, catalyst and non-protonic solvent It is reacted, post-processing obtains compound A-4a；

Compound A-4a is carried out hydrogenation reduction by step 4 in the presence of reducing agent and alcoholic solvent, and post-processing is produced Product compound 2- (2- oxazolyl) ethamine (formula A-a).

Preparation method route is as follows:

In another better embodiment of the invention, the preparation method of 2- (oxazolyl) ethamine is specially 2- (4- Oxazolyl) ethamine (formula A-b) preparation method,

Specifically includes the following steps:

Compound A-1b is carried out reduction reaction by step 1 in the presence of reducing agent and alcoholic solvent, and post-processing obtains compound A-2b；

Step 2 reacts compound A-2b in the presence of methylsufonyl chloride, organic base and organic solvent, rear to locate Reason obtains compound A-3b；

Step 3, by compound A-3b in the presence of trimethylsilyl cyanide, inorganic base, catalyst and non-protonic solvent It is reacted, post-processing obtains compound A-4b；

Compound A-4b is carried out hydrogenation reduction by step 4 in the presence of reducing agent and alcoholic solvent, and post-processing is produced Product compound 2- (4- oxazolyl) ethamine (formula A-b).

Preparation method route is as follows:

In aforesaid operations, post-processing includes but is not limited to plus water quenching goes out, stirs, extracting, the transfer of liquid or solid, water Wash, alkali cleaning, pickling, filtering, ultrafiltration, loop ultrafiltration, dilution, concentration, drying, column chromatography, freeze-drying etc. operation, or add water quenching It goes out, stir, extracting, the transfer of liquid or solid, washing, alkali cleaning, pickling, filtering, ultrafiltration, loop ultrafiltration, dilution, concentration, doing The combination of one or more of the operations such as dry, column chromatography, freeze-drying.

In better embodiment of the invention, the filtering refers to the process of solid in reaction solution and liquid separation, Including being commonly separated by filtration, being centrifugated；Wherein, described to be commonly separated by filtration including but not limited to using filter cloth, filter membrane, filter paper Deng；

The concentration, which refers to the process of, removes liquid solvent, including is concentrated under reduced pressure, normal pressure concentration etc.；

The step, solvent, reagent, filtering, concentration in the preparation method of above-mentioned 2- (oxazolyl) ethamine of the present invention, point From, purifying etc. can in any combination/split, can be achieved the object of the invention.

Compared with prior art, the preparation method of 2- of the invention (oxazolyl) ethamine, avoids using highly basic n-BuLi Equal lithium reagents, effectively prevent the open loop side reaction of oxazole ring, reproducible, conversion ratio and high income, easy purification, obtained 2- (oxazolyl) ethylamine compounds good product quality, is conducive to industrial applications；

The preparation method of 2- (oxazolyl) ethamine of the invention is avoided using hazardous chemical and high-temperature and high-pressure conditions, side Method route reaction condition is mild, highly-safe, reduces the security risk to operator, reduces the safe operation etc. of production Grade, it is environmentally protective, while totle drilling cost is effectively reduced, it is advantageously implemented industrial amplification production；

The preparation method of 2- (oxazolyl) ethamine of the invention, compensating for literature method disclosed in the prior art cannot prepare The defect of particular compound 2- (4- oxazolyl) ethamine (CAS No.227475-42-5) product is obtained, using above-mentioned preparation method 2- (2- oxazolyl) ethamine and 2- (4- oxazolyl) ethylamine compounds can be obtained, filled up the conjunction of 2- (4- oxazolyl) ethylamine compounds At blank, be conducive to the application of the preparation of chemical synthesis compound.

In conclusion the preparation method of 2- (oxazolyl) ethamine of the present invention, effectively avoids oxazole open loop side reaction, repeatability It is good, conversion ratio and high income, easy purification；Reaction condition is mild, highly-safe, reduces the security risk to operator, reduces The safe operation grade of production, it is environmentally protective；Obtained 2- (oxazolyl) ethamine product purity is high, high-quality, is conducive to reality Now industrialize.

Make below with reference to technical effect of the embodiment to design of the invention, specific technical solution and generation further Illustrate, to fully understand the purposes, features and effects of the present invention.

Specific embodiment

Multiple preferred embodiments of the invention introduced below keep its technology contents more clear and are easy to understand.The present invention It can be emerged from by many various forms of embodiments, these embodiments are exemplary description, protection model of the invention Enclose the embodiment for being not limited only to mention in text.

If there is test method without specific conditions, usually according to normal condition, such as instructions book or handbook Implemented.