阅读说明：本技术 乙基-3-氧亚基-1-氧杂-4-氮杂螺[5.5]十一烷-9-甲酸基酯的合成方法 (Synthesis method of ethyl-3-oxylidene-1-oxa-4-azaspiro [5.5] undecane-9-formic acid ester ) 是由 张大为 周强 高明飞 姚宝元 兰倩倩 赵廷 王曦 卫维 魏昕睿 谭汝鹏 贾涛 于 2020-05-20 设计创作，主要内容包括：本发明涉及一种乙基-3-氧亚基-1-氧杂-4-氮杂螺[5.5]十一烷-9-甲酸基酯的合成方法,主要解决目前没有适合工业化合成方法的技术问题。本发明分三步,第一步,首先由化合物1在溶剂二氯甲烷中加入三乙胺,氯乙酰氯反应得到化合物2,第二步,化合物2与碘化钠在丙酮中反应得到化合物3,第三步,化合物3与叔丁醇钾在叔丁醇和四氢呋喃中反应得到最终化合物4。反应式如下：<Image he="139" wi="559" file="697125DEST_PATH_IMAGE002.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>。(The invention relates to an ethyl-3-oxylidene-1-oxa-4-azaspiro [5.5]A synthesis method of undecane-9-formic acid ester mainly solves the technical problem that no industrial synthesis method is available at present. The method comprises three steps, wherein in the first step, triethylamine and chloroacetyl chloride are added into a solvent dichloromethane from a compound 1 to react to obtain a compound 2, in the second step, the compound 2 and sodium iodide react in acetone to obtain a compound 3, and in the third step, the compound 3 and potassium tert-butoxide react in tert-butyl alcohol and tetrahydrofuran to obtain a final compound 4. The reaction formula is as follows: 。)

1. Ethyl-3-oxylidene-1-oxa-4-azaspiro [5.5]The synthesis method of the undecane-9-formic acid ester is characterized by comprising the following steps: the method comprises three steps, wherein in the first step, triethylamine and chloroacetyl chloride are added into a solvent dichloromethane from a compound 1 to react to obtain a compound 2, in the second step, the compound 2 and sodium iodide react in acetone to obtain a compound 3, and in the third step, the compound 3 and potassium tert-butoxide react in tert-butyl alcohol and tetrahydrofuran to obtain a final compound 4; the reaction formula is as follows:。

2. the method for synthesizing ethyl-3-oxoidene-1-oxa-4-azaspiro [5.5] undecane-9-carboxylic acid ester according to claim 1, wherein: the reaction temperature in the first step was room temperature and the reaction time was 2 hours.

3. The method for synthesizing ethyl-3-oxoidene-1-oxa-4-azaspiro [5.5] undecane-9-carboxylic acid ester according to claim 1, wherein: the second step reaction temperature was 50 ℃ and the reaction time was 4 hours.

4. The method for synthesizing ethyl-3-oxoidene-1-oxa-4-azaspiro [5.5] undecane-9-carboxylic acid ester according to claim 1, wherein: the third step is at 120 deg.C for 4 hr.

Technical Field

The invention relates to a synthetic method of a compound ethyl-3-oxyidene-1-oxa-4-azaspiro [5.5] undecane-9-formic acid ester.

Background

The compound ethyl-3-oxylidene-1-oxa-4-azaspiro [5.5] undecane-9-formic acid ester (CAS: 1422344-43-1) and related derivatives have wide application in pharmaceutical chemistry and organic synthesis. At present, the synthesis method of ethyl-3-oxylidene-1-oxa-4-azaspiro [5.5] undecane-9-formic acid ester is only reported in documents. Therefore, it is necessary to develop a synthesis method which has easily available raw materials, convenient operation, easy control of reaction, proper overall yield and suitability for industrial production.

Disclosure of Invention

The invention aims to develop a synthetic method of ethyl 3-oxyidene-1-oxa-4-azaspiro [5.5] undecane-9-formic acid ester, which has the advantages of easily obtained raw materials, convenient operation, easy control of reaction and higher yield. Mainly solves the technical problem that no industrial synthesis method is available at present.

The technical scheme of the invention is as follows: the invention relates to a synthesis method of ethyl-3-oxylidene-1-oxa-4-azaspiro [5.5] undecane-9-formylate, which comprises three steps, wherein in the first step, triethylamine and chloroacetyl chloride are added into a solvent dichloromethane from a compound 1 to react to obtain a compound 2, in the second step, the compound 2 and sodium iodide are reacted in acetone to obtain a compound 3, and in the third step, the compound 3 and potassium tert-butoxide are reacted in tert-butyl alcohol and tetrahydrofuran to obtain a final compound 4. The reaction formula is as follows:

the first step is reaction temperature of room temperature for 2 hours; the second step is that the reaction temperature is 50 ℃ and the reaction time is 4 hours; the third step is reaction temperature of 120 ℃ for 4 hours.

The Chinese explanation of the invention is as follows: TLC: thin layer chromatography.

The invention has the beneficial effects that: the reaction process of the invention has reasonable design, adopts the raw material ethyl 4- (aminomethyl) -4-hydroxycyclohexyl formate which is easy to obtain and can be produced in large scale, and synthesizes ethyl 3-oxyidene-1-oxa-4-azaspiro [5.5] undecane-9-formate through three steps.

Detailed Description

The reaction formula of the invention is as follows: