CN109232476B - Method for preparing N-phenyl-3-morpholine propionamide - Google Patents
Method for preparing N-phenyl-3-morpholine propionamide Download PDFInfo
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- CN109232476B CN109232476B CN201811311940.7A CN201811311940A CN109232476B CN 109232476 B CN109232476 B CN 109232476B CN 201811311940 A CN201811311940 A CN 201811311940A CN 109232476 B CN109232476 B CN 109232476B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/145—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/15—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
Abstract
The invention relates to the technical field of fine chemical engineering, and discloses a method for preparing N-phenyl-3-morpholine propionamide. The method comprises the following specific steps: n-phenyl-3-methylthiopropanamide, morpholine, 1-chloromethyl-4-fluoro-1, 4-diazabicyclo [2.2.2] octane bis (tetrafluoroborate) and sodium carbonate are stirred and react for 12 hours in an organic solvent 1, 4-dioxane at 100 ℃ to obtain the N-phenyl-3-morpholine propanamide. Compared with the prior art, the method has the advantages of simple operation, rapidness and high efficiency, does not need to use 3-chloropropionyl chloride which is toxic, easy to corrode and easy to volatilize as a raw material, and is environment-friendly.
Description
Technical Field
The invention belongs to the field of fine chemical engineering, and relates to a method for preparing N-phenyl-3-morpholine propionamide.
Background
N-phenyl-3-morpholine propionamide is an important organic chemical raw material, and the compound is not only an important intermediate for synthesizing various active biomolecules or medicaments, but also widely applied to the synthesis of various fine chemicals.
Currently, the method for synthesizing N-phenyl-3-morpholinopropionamide is as follows:
the first method comprises the following steps: the N-phenyl acrylamide and the morpholine are used as initial raw materials and react for 4 days under the action of alkali to obtain the target product N-phenyl-3-morpholine propionamide. The disadvantage of this synthesis is that the reaction time is relatively long, requiring four days.
And the second method comprises the following steps: 3-chloropropionyl chloride, aniline and morpholine are used as reaction raw materials, and a target product N-phenyl-3-morpholine propionamide is prepared through two-step reaction under the action of alkali. The disadvantages of such synthetic methods are: 3-chloropropionyl chloride with toxicity and irritation is used as a reaction raw material, the prior environment-friendly technical characteristics are not met, a target product is synthesized by two-step reaction, and the operation is relatively complex. The yield of the target product of the reaction is only 13 percent, the yield is too low, and the synthesis application value is not high.
Therefore, it is necessary to develop a synthetic method which is low in toxicity, environment-friendly, simple in operation, and fast and efficient.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a method for preparing N-phenyl-3-morpholine propionamide, which is rapid, high in efficiency, simple, novel, simple and convenient to operate and environment-friendly.
The reaction steps for synthesizing the N-phenyl-3-morpholine propionamide comprise: sequentially adding N-phenyl-3-methylthiopropanamide, morpholine, 1-chloromethyl-4-fluoro-1, 4-diazabicyclo [2.2.2] octane bis (tetrafluoroborate) and sodium carbonate into a round-bottom flask containing a reaction solvent, violently stirring for 12 hours at 100 ℃, and after the reaction is finished, sequentially concentrating the reaction solution and carrying out column chromatography separation to obtain the N-phenyl-3-morpholine propanamide.
The solvent in the invention is 1, 4-dioxane.
The concentration of the reaction system in the present invention is 0.1 to 1.0 mol/l, preferably 0.5 mol/l.
In the invention, the molar ratio of N-phenyl-3-methylthiopropanamide, morpholine, 1-chloromethyl-4-fluoro-1, 4-diazabicyclo [2.2.2] octane bis (tetrafluoroborate) salt to sodium carbonate is 1: 2: 1: 1.
the reaction temperature in the invention is 80-120 ℃, preferably 100 ℃.
The reaction time in the invention is 8-20 hours, preferably 12 hours.
Detailed Description
The following examples will help illustrate the invention, but do not limit its scope.
Specific example 1:
in a 100mL round bottom flask were added N-phenyl-3-methylthiopropionamide (10mmol,1.95g), morpholine (20mmol,1.74g), 1-chloromethyl-4-fluoro-1, 4-diazabicyclo [2.2.2] octane bis (tetrafluoroborate) salt (10mmol,1.78g), sodium carbonate (10mmol,1.06g), and 20mL of 1, 4-dioxane in that order, the reaction temperature was controlled at 100 degrees Celsius, and the reaction was stirred vigorously for 12 hours. After the reaction, the reaction solution was cooled to room temperature, and concentration and column chromatography separation were sequentially performed to obtain N-phenyl-3-morpholinopropionamide (1.87g, 80%).
The reaction involves the following equation:
specific example 2:
in a 100mL round bottom flask were added N-phenyl-3-methylthiopropionamide (10mmol,1.95g), morpholine (20mmol,1.74g), 1-chloromethyl-4-fluoro-1, 4-diazabicyclo [2.2.2] octane bis (tetrafluoroborate) salt (10mmol,1.78g), sodium carbonate (10mmol,1.06g), and 20mL of 1, 4-dioxane in that order, the reaction temperature was controlled at 80 degrees Celsius, and the reaction was stirred vigorously for 12 hours. After the reaction, the reaction solution was cooled to room temperature, and concentration and column chromatography separation were sequentially performed to obtain N-phenyl-3-morpholinopropionamide (1.52g, 65%).
The reaction involves the following equation:
the foregoing describes alternative embodiments of the invention to teach those skilled in the art how to make and reproduce the invention. Some conventional technical aspects have been simplified and omitted for the purpose of teaching the inventive arrangements. Those skilled in the art will appreciate variations from this aspect that fall within the scope of the invention.
Claims (7)
1. A method for preparing N-phenyl-3-morpholine propionamide is carried out according to the following steps: adding N-phenyl-3-methylthiopropionamide, morpholine, 1-chloromethyl-4-fluoro-1, 4-diazabicyclo [2.2.2] octane bis (tetrafluoroborate) salt and sodium carbonate into an organic solvent, and heating and violently stirring to obtain the N-phenyl-3-morpholine propionamide.
2. The method as claimed in claim 1, further comprising reduced pressure distillation after the reaction, column chromatography separation and collection of the target product.
3. The method of claim 1, wherein: the reaction temperature is 80-120 ℃.
4. The method of claim 1, wherein: the reaction time is 8-20 hours.
5. The method of claim 1, wherein: the adding amounts of N-phenyl-3-methylthiopropanamide, morpholine, 1-chloromethyl-4-fluoro-1, 4-diazabicyclo [2.2.2] octane bis (tetrafluoroborate) and sodium carbonate are as follows according to the molar ratio of 1: 2: 1: 1, standard addition.
6. The method of claim 1, wherein: the organic solvent used in the reaction is 1, 4-dioxane.
7. The method of claim 1, wherein: the concentration of the reaction system is 0.1-1.0 mol/L.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201811311940.7A CN109232476B (en) | 2018-11-06 | 2018-11-06 | Method for preparing N-phenyl-3-morpholine propionamide |
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| CN201811311940.7A CN109232476B (en) | 2018-11-06 | 2018-11-06 | Method for preparing N-phenyl-3-morpholine propionamide |
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| CN109232476A CN109232476A (en) | 2019-01-18 |
| CN109232476B true CN109232476B (en) | 2020-06-26 |
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| CN110563599B (en) * | 2019-09-02 | 2022-03-22 | 常州大学 | Method for preparing 3-methoxy-N-phenylpropionamide |
| CN111848464B (en) * | 2020-07-03 | 2022-03-25 | 常州大学 | Method for preparing 2- (methylsulfinyl) benzoic acid |
| CN113135865B (en) * | 2021-04-01 | 2022-07-05 | 常州大学 | Method for preparing N-phenyl-3- (benzotriazole-1-yl) propionamide |
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| AR053358A1 (en) * | 2005-04-15 | 2007-05-02 | Cancer Rec Tech Ltd | DNA INHIBITORS - PK |
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