CN101735165A - Preparation method of 3-morpholone - Google Patents
Preparation method of 3-morpholone Download PDFInfo
- Publication number
- CN101735165A CN101735165A CN201010017978A CN201010017978A CN101735165A CN 101735165 A CN101735165 A CN 101735165A CN 201010017978 A CN201010017978 A CN 201010017978A CN 201010017978 A CN201010017978 A CN 201010017978A CN 101735165 A CN101735165 A CN 101735165A
- Authority
- CN
- China
- Prior art keywords
- preparation
- solvent
- sodium
- morpholone mai
- morpholone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of 3-morpholone, which comprises the steps of: firstly, under the protection of nitrogen, cooling ethanolamine and organic solvent or a mixed solvent to below 0--10 DEG C under the action of alkali or mixed alkali, dropwise adding ethyl chloroacetate, controlling the temperature below 0--6 DEG C; and secondly, raising the temperature to 30-80 DEG C, stirring for 0.2-2h, filtering, washing solid with a solvent, merging mother solutions, evaporating to remove the solvent, and recrystallizing to obtain the pure product of the 3-morpholone. The preparation method has the characteristics of easy obtaining of raw materials, simple process, low cost, high product purity, low content of side products and the like. The yield of the 3-morpholone is 20-80 percent. The invention is suitable for large-scale industrialized production.
Description
Technical field
The present invention relates to a kind of preparation method of 3-morpholone mai, belong to organic synthesis and prepare chemical field.
Background technology
The 3-morpholone mai is a kind of very important organic intermediate, is widely used in medication chemistry, fields such as polymer chemistry.
The preparation method of 3-morpholone mai mainly contains two kinds: 1. make solvent with dioxane, under the effect of sodium Metal 99.5, thanomin and ethyl chloroacetate prepare 3-morpholone mai [Bulletin de la Societe Chimiquede France, 287-9; 1953]; 2. sodium hydride is made alkali, and thanomin and Mono Chloro Acetic Acid second prepare 3-morpholone mai [WO 2006055951] in dioxane.
The first method yield is low, and by product is many, and industrial value is little.The second method yield is also low, and by product is many, and is to prepare by column chromatography, and industrial value is little.
Summary of the invention
The objective of the invention is to overcome the deficiency that prior art exists, provide a kind of raw material be easy to get, easy to operate, be suitable for the method that large-scale industrial production prepares the 3-morpholone mai.
Purpose of the present invention is achieved through the following technical solutions:
The preparation method of 3-morpholone mai, characteristics are: at first nitrogen protection, under alkali or mixed base effect; thanomin and organic solvent or mixed solvent are cooled under 0～-10 ℃; drip chloroethene ester ethyl ester, temperature control is warming up to 30～80 ℃ then and stirs 0.2～2h under 0～-6 ℃; filter; the solid solvent wash merges mother liquor, and steaming desolventizes; recrystallization obtains the pure product of 3-morpholone mai.
Further, the preparation method of above-mentioned 3-morpholone mai, described alkali is a kind of in sodium Metal 99.5, sodium hydride, potassium tert.-butoxide, sodium tert-butoxide, the sodium isopropylate, and described mixed base is a mixture several in sodium Metal 99.5, sodium hydride, potassium tert.-butoxide, sodium tert-butoxide, the sodium isopropylate.
Further, the preparation method of above-mentioned 3-morpholone mai, described organic solvent is a kind of in toluene, Virahol, the trimethyl carbinol, ethanol, the methyl alcohol, described mixed solvent is a mixed solvent several in toluene, Virahol, the trimethyl carbinol, ethanol, the methyl alcohol.
Further, the preparation method of above-mentioned 3-morpholone mai, the mol ratio of described alkali or mixed base and thanomin are 0.5～1.5.
Again further, the preparation method of above-mentioned 3-morpholone mai, the mol ratio of described chloroethene ester ethyl ester and thanomin is 0.5～1.5.
Again further, the preparation method of above-mentioned 3-morpholone mai, the solvent that described recrystallization is used is one or more the mixed solvent in toluene, Virahol, the trimethyl carbinol, ethanol, methyl alcohol, ethyl acetate, the sherwood oil.
Substantive distinguishing features and obvious improvement that technical solution of the present invention is outstanding are mainly reflected in:
The preparation method of 3-morpholone mai of the present invention has characteristics such as raw material is easy to get, technology is simple, cost is low, product purity is high, by-products content is low, and the yield 20～80% of 3-morpholone mai is suitable for large-scale industrial production.
Description of drawings
Below in conjunction with accompanying drawing technical solution of the present invention is described further:
Fig. 1: reaction synoptic diagram of the present invention.
Embodiment
The preparation method of 3-morpholone mai, as shown in Figure 1, at first nitrogen protection; under alkali or mixed base effect, thanomin and organic solvent or mixed solvent are cooled under 0～-10 ℃, drip chloroethene ester ethyl ester; temperature control is under 0～-6 ℃; be warming up to 30～80 ℃ then and stir 0.2～2h, filter the solid solvent wash; merge mother liquor; steaming desolventizes, and recrystallization obtains the pure product of 3-morpholone mai.
Wherein, alkali is a kind of in sodium Metal 99.5, sodium hydride, potassium tert.-butoxide, sodium tert-butoxide, the sodium isopropylate, and mixed base is a mixture several in sodium Metal 99.5, sodium hydride, potassium tert.-butoxide, sodium tert-butoxide, the sodium isopropylate.Organic solvent is a kind of in toluene, Virahol, the trimethyl carbinol, ethanol, the methyl alcohol, and mixed solvent is a mixed solvent several in toluene, Virahol, the trimethyl carbinol, ethanol, the methyl alcohol.The mol ratio of alkali or mixed base and thanomin is 0.5～1.5, and optimum mole ratio is 1: 1.The mol ratio of chloroethene ester ethyl ester and thanomin is 0.5～1.5, and optimum mole ratio is 1: 0.9.The solvent that recrystallization is used is one or more the mixed solvent in toluene, Virahol, the trimethyl carbinol, ethanol, methyl alcohol, ethyl acetate, the sherwood oil.
Embodiment 1:
Nitrogen protection joins the 11.5g sodium Metal 99.5 in the solution that contains 30.5g thanomin and 500ml Virahol in batches, is warming up to 50 ℃; be stirred to the sodium dissolving, reaction solution be cooled under 0～-10 ℃ Dropwise 5 5.2g chloroethene ester ethyl ester; temperature control is warming up to 30～80 ℃ of degree then and stirs 0.2～2h under 0～-6 ℃, filters; the solid solvent wash; merge mother liquor, steaming desolventizes, and gets the pure product of 34.1g 3-morpholone mai with ethyl acetate and Virahol recrystallization; yield 75%, GC purity 99.5%.
Ultimate analysis: theoretical value: C, 47.52; H, 6.98, N, 13.85, O, 31.65.Measured value: C, 47.54; H, 6.99, N, 13.83, O, 31.64.
Need to prove that the bound value and the interval value of the alkali that the present invention is used and the mol ratio of thanomin can both be realized the present invention; The bound value and the interval value of the used thanomin and the mol ratio of ethyl chloroacetate can both be realized the present invention; Alkali is that a kind of or mixed base such as sodium Metal 99.5, sodium hydride, potassium tert.-butoxide, sodium tert-butoxide, sodium isopropylate also can be realized the present invention; Just do not enumerate embodiment one by one at this.
In sum, 3-morpholone mai preparation method of the present invention has characteristics such as raw material is easy to get, technology is simple, cost is low, product purity is high, by-products content is low, and the yield 20～80% of 3-morpholone mai is suitable for large-scale industrial production.
What need understand is: the above only is a preferred implementation of the present invention; for those skilled in the art; under the prerequisite that does not break away from the principle of the invention, can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (6)
1.3-the preparation method of morpholone mai is characterized in that: at first nitrogen protection, under alkali or mixed base effect; thanomin and organic solvent or mixed solvent are cooled under 0～-10 ℃; drip chloroethene ester ethyl ester, temperature control is warming up to 30～80 ℃ then and stirs 0.2～2h under 0～-6 ℃; filter; the solid solvent wash merges mother liquor, and steaming desolventizes; recrystallization obtains the pure product of 3-morpholone mai.
2. the preparation method of 3-morpholone mai according to claim 1, it is characterized in that: described alkali is a kind of in sodium Metal 99.5, sodium hydride, potassium tert.-butoxide, sodium tert-butoxide, the sodium isopropylate, and described mixed base is a mixture several in sodium Metal 99.5, sodium hydride, potassium tert.-butoxide, sodium tert-butoxide, the sodium isopropylate.
3. the preparation method of 3-morpholone mai according to claim 1, it is characterized in that: described organic solvent is a kind of in toluene, Virahol, the trimethyl carbinol, ethanol, the methyl alcohol, and described mixed solvent is a mixed solvent several in toluene, Virahol, the trimethyl carbinol, ethanol, the methyl alcohol.
4. the preparation method of 3-morpholone mai according to claim 1 is characterized in that: the mol ratio of described alkali or mixed base and thanomin is 0.5～1.5.
5. the preparation method of 3-morpholone mai according to claim 1 is characterized in that: the mol ratio of described chloroethene ester ethyl ester and thanomin is 0.5～1.5.
6. the preparation method of 3-morpholone mai according to claim 1 is characterized in that: the solvent that described recrystallization is used is one or more the mixed solvent in toluene, Virahol, the trimethyl carbinol, ethanol, methyl alcohol, ethyl acetate, the sherwood oil.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010017978A CN101735165A (en) | 2010-01-19 | 2010-01-19 | Preparation method of 3-morpholone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010017978A CN101735165A (en) | 2010-01-19 | 2010-01-19 | Preparation method of 3-morpholone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101735165A true CN101735165A (en) | 2010-06-16 |
Family
ID=42459246
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010017978A Pending CN101735165A (en) | 2010-01-19 | 2010-01-19 | Preparation method of 3-morpholone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101735165A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103804316A (en) * | 2012-11-13 | 2014-05-21 | 天津药物研究院 | Preparation method of (2RS, 3RS)-6-[a-(2-ethoxyl phenoxyl) benzyl] morpholine-3-one (I) |
| CN105753804A (en) * | 2016-04-15 | 2016-07-13 | 大连信科化工有限公司 | Method of preparing 3-morpholinone |
| CN108586377A (en) * | 2018-06-07 | 2018-09-28 | 上海科利生物医药有限公司 | A kind of preparation method of 3- morpholones |
| CN109422703A (en) * | 2017-08-29 | 2019-03-05 | 浙江京新药业股份有限公司 | A method of preparing 3- morpholone |
-
2010
- 2010-01-19 CN CN201010017978A patent/CN101735165A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103804316A (en) * | 2012-11-13 | 2014-05-21 | 天津药物研究院 | Preparation method of (2RS, 3RS)-6-[a-(2-ethoxyl phenoxyl) benzyl] morpholine-3-one (I) |
| CN105753804A (en) * | 2016-04-15 | 2016-07-13 | 大连信科化工有限公司 | Method of preparing 3-morpholinone |
| CN109422703A (en) * | 2017-08-29 | 2019-03-05 | 浙江京新药业股份有限公司 | A method of preparing 3- morpholone |
| CN108586377A (en) * | 2018-06-07 | 2018-09-28 | 上海科利生物医药有限公司 | A kind of preparation method of 3- morpholones |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108129288B (en) | Synthesis method of trans-3-hydroxycyclobutylformic acid | |
| CN104876995A (en) | A preparing method of a chenodeoxycholic acid derivative | |
| CN101735165A (en) | Preparation method of 3-morpholone | |
| CN104262318A (en) | Method for preparing olopatadine hydrochloride | |
| AU2018250429B2 (en) | Method for preparing azoxystrobin | |
| CN103044468B (en) | Preparation method of N-(2-pyrazine carbonyl)-L-phenylalanine-L- leucine boracic acid | |
| CN102391128A (en) | Production method of antibiotic pharmaceutical intermediate mono-p-nitro benzyl malonate | |
| CN102146113B (en) | Method for synthesizing 16 alpha-hydroxy prednisolone | |
| CN102399149A (en) | Preparation method of antiviral drug tenofovir disoproxil fumarate intermediate chloromethyl isopropyl carbonate | |
| CN104098462B (en) | The method for splitting of the diphenyl-propionic acid racemoid of 2 hydroxyl, 3 methoxyl group 3,3 | |
| CN110368987B (en) | Preparation method and application of tree-like loofah sponge supported ionic liquid catalyst | |
| CN101709050B (en) | New method for synthesizing 2, 5-dichloropyridine | |
| CN109438237B (en) | Preparation method of 3-ethoxy ethyl acrylate | |
| CN102180843A (en) | Preparation method of 2-(2-amino-4-thiazolyl)-2(Z)-triphenylmethoxy imidoacetic acid | |
| CN102070650A (en) | Preparation method for levofloxacin-N-oxide | |
| CN104961724A (en) | Advanced production technology for obtaining highly pure desloratadine | |
| CN102391139A (en) | Energy-saving and environmentally-friendly process for synthesizing alkyl betaine | |
| CN103506140B (en) | Lactic acid catalyst for synthesizing and synthetic method | |
| CN108117490B (en) | Preparation method of p-nitrobenzyl alcohol | |
| CN104447528B (en) | The preparation method of pyridine-2,3-diethyl dicarboxylate | |
| CN103570670B (en) | The preparation method of 2-((4R, 6S)-6-chloromethyl-2-alkyl-1,3-dioxane-4-base) methyl acetate | |
| CN106478558B (en) | A kind of synthetic method of 4- methylol-dihydro-furan -2 (3H) -one | |
| CN112979560B (en) | Method for preparing uracil | |
| CN108069897B (en) | Method for synthesizing nicotinic acid by using carbon dioxide | |
| CN101328146A (en) | Preparation of 5-cyano imino stilbene |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20100616 |