CN101293850B - Method for preparing 3-N,N-dimethylamino-ethyl acrylate - Google Patents
Method for preparing 3-N,N-dimethylamino-ethyl acrylate Download PDFInfo
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- CN101293850B CN101293850B CN2008101240242A CN200810124024A CN101293850B CN 101293850 B CN101293850 B CN 101293850B CN 2008101240242 A CN2008101240242 A CN 2008101240242A CN 200810124024 A CN200810124024 A CN 200810124024A CN 101293850 B CN101293850 B CN 101293850B
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Abstract
The invention provides a preparation method of 3-N,N-dimethylaminoethyl acrylate. The preparation process comprises adding diethyl sulfate to dimethylformamide (DMF) at a molar ratio of 1:(1.1-1.3) for reacting to generate condensated salt; mixing with diethyl malonate, solvent and catalyst, heating until refluxing and reacting for 3-10 hours, and cooling to room temperature; filtering to remove the salt, washing the filtrate with water, mixing the organic layer, and depressing and distilling to remove solvent; and high vacuum distilling the residue, and collecting fraction of 80-85 DEC C /5mmHg. The obtained 3-N,N-dimethylaminoethyl acrylate has yield and purity higher than that of optimal values in prior art.
Description
Technical field
The present invention relates to prepare 3-N, the process method of N-dimethylamino ethyl propenoate belongs to the fine chemical technology field.
Background technology
3-N, (Ethyl-3-(N, N-dimethylamine arcrylate or 3-Dimethylamino-acrylic acid ethyl ester) is as the midbody of QNS Moxifloxacin for N-dimethylamino ethyl propenoate.3-N; The compound method of N-dimethylamino ethyl propenoate has: 1. with DMF (N; Dinethylformamide) and oxyethyl group acetylene be that raw material gets through addition reaction, 20 ℃ the reaction 20 days, yield is 25% (Recueil des Travaux Chimiques des Pays-BAS; 85 (9-10), 929-51; 1966); 2. be that 170 ℃ of reactions of raw material got yield 88% (Chemische Berichte, 104 (9), 2709-26 in 20 hours with spy-tert.-butoxy-2-dimethylamino methane and ETHYLE ACETATE; 1971); 3. process monopotassium salt with KOH earlier with ethyl propenoate or ethyl malonate, make with DMF-methyl-sulfate condensation reactant salt, yield is up to 88% (WO2000000460); 4. with N, N-dimethylbenzyl ethyl propenoate is a raw material, is catalyzer with the zinc bromide, is that solvent makes with first cyanogen, yield 29% (TetrahedronLetters, 46 (1), 69-74; 2004).
Can show from above-mentioned prior preparation method, be that method time of raw material is oversize with DMF and oxyethyl group acetylene, and yield is low, is inappropriate for industrialization.With N, N-dimethylbenzyl ethyl propenoate is the method for raw material, equally also is that yield is too low, and uses first cyanogen to be solvent, and toxicity is big.With spy-tert.-butoxy-2-dimethylamino methane and ETHYLE ACETATE is that high time of method temperature of raw material is long, and raw materials cost is high, and energy consumption is high.The WO2000000460 disclosed method then needs two-step reaction, must process the malonic ester monopotassium salt earlier, and this process is difficult to control, and with hypertoxic methyl-sulfate as raw material, poor stability.
In sum, present 3-N, no matter the preparation method of N dimethylamino ethyl propenoate is on used raw material, all exists defective on the still concrete operational condition, is not suitable for industrialization.
Summary of the invention
The purpose of this invention is to provide preparation 3-N, the method for N-dimethylamino ethyl propenoate is intended to effectively simplify preparation technology, reduces production costs, and improves the yield and the purity of finished product.
The object of the invention is realized through following technical scheme:
3-N, the preparation method of N-dimethylamino ethyl propenoate may further comprise the steps---
1) (1.1～1.3) in molar ratio: 1 consumption, in DMF, add ethyl sulfate, controlled temperature is incubated 2～5 hours at 80～90 ℃, generates DMF-ethyl sulfate condensation salts solution;
2) with DMF-ethyl sulfate condensation salts solution and ethyl malonate, solvent, catalyst mix, be warming up to and reflux and reacted 3～10 hours, reduce to room temperature then;
3) reaction is cooled to 10～20 ℃ after finishing, filter, and filtrating washing back layering, collected organic layer, high vacuum underpressure distillation again behind the concentrating under reduced pressure, the cut of collecting 80～85 ℃/5mmHg is finished product.
The object of the invention also can further realize through following technical measures:
Above-mentioned 3-N, the preparation method of N-dimethylamino ethyl propenoate, step 2) in solvent be benzene, toluene, orthodichlorobenzene, ethylene dichloride.
Further, above-mentioned 3-N, the preparation method of N-dimethylamino ethyl propenoate, step 2) in catalyzer be pyridine or pyridine-piperidines mixture.
Further; Above-mentioned 3-N; The preparation method of N-dimethylamino ethyl propenoate, step 2) weight ratio of ethyl malonate and DMF-ethyl sulfate condensation salts solution is 1 in: (1～1.3), the mol ratio of ethyl malonate and catalyzer are 1: (0.9～1.2).
Again further, above-mentioned 3-N, the preparation method of N-dimethylamino ethyl propenoate, in the step 3), the temperature of concentrating under reduced pressure is 40～70 ℃, gauge pressure is-0.09～-0.098MPa; The temperature of high vacuum underpressure distillation is 90～100 ℃, and vacuum tightness is more than the 5mmHg.
Substantive distinguishing features and obvious improvement that technical scheme of the present invention is outstanding are mainly reflected in:
The present invention adopts hypotoxic ethyl sulfate to replace the methyl-sulfate of severe toxicity; With the ethyl malonate is raw material; Make 3-N with DMF-ethyl sulfate condensation salt condensation single step reaction under catalyst action; N-dimethylamino ethyl propenoate, the yield of product and purity all reach the prior art optimum value.Its preparation process is simple and easy to do, and temperature of reaction is low, and the time is short, and intermediate product need not to separate, energy-conserving and environment-protective, and production cost is low, and good product quality is easy to accomplish scale production.
Embodiment
The present invention is through the synthetic 3-N of the method for single step reaction, and N-dimethylamino ethyl propenoate adopts hypotoxic ethyl sulfate to replace the methyl-sulfate of severe toxicity; Temperature of reaction is low, and the time is short, and intermediate product need not to separate; Condition is easy to control, and is easy and simple to handle, and concrete detailed technological process is:
1. in flask, add DMF, be warming up to 80～90 ℃, slowly add ethyl sulfate; Molar ratio=(1.1～1.3): 1,80～90 ℃ of temperature controls add the back insulation reaction; Soaking time is 2～5 hours, generates DMF-ethyl sulfate condensation salts solution, and reaction is reduced to room temperature after finishing;
2. in above-mentioned DMF-ethyl sulfate condensation salts solution, add ethyl malonate, solvent, catalyzer; The weight ratio of ethyl malonate and DMF-ethyl sulfate condensation salts solution is 1: (1～1.3); The mol ratio of ethyl malonate and catalyzer is 1: (0.9～1.2); Be warming up to the backflow afterreaction 3～10 hours, the time of insulation reaction looks the difference of solvent and changes to some extent, reduces to room temperature;
3. be cooled to 10～20 ℃ after reaction finishes, filter, after the filtrate water washing, merge organic layer, first concentrating under reduced pressure, the temperature of concentrating under reduced pressure is 40～70 ℃, gauge pressure is-0.09～-0.098MPa; High vacuum underpressure distillation again behind the concentrating under reduced pressure, the temperature of high vacuum underpressure distillation are 90～100 ℃, and vacuum tightness is more than the 5mmHg; The cut of collecting 80～85 ℃/5mmHg is finished product.
Further specify technical scheme of the present invention through specific embodiment below.
Embodiment 1:
In 2000ml four neck flasks, add DMF120.6g (1.65mol), be warming up to 80 ℃, slowly add ethyl sulfate 231.3g (1.5mol), 80～90 ℃ of controlled temperature added the back insulation reaction 2 hours, and reaction is cooled to room temperature after finishing.
In flask, add toluene 900ml, ethyl malonate 240.2g (1.5mol), pyridine 118.6g (1.5mol), be warming up to backflow, insulation reaction 5 hours; Reaction is cooled to 10～20 ℃ after finishing, and filters; To filtrate with after the 500ml washing three times, collected organic layer, concentrating under reduced pressure reclaims solvent, and the temperature of concentrating under reduced pressure is 60 ℃, and gauge pressure is-0.098MPa; Carry out underpressure distillation again, the temperature of underpressure distillation is 90～100 ℃, and vacuum tightness is more than the 5mmHg, collects the cut 154.6g of 80～85 ℃/5mmHg, is product; Content: 96.5% (HPLC).
Embodiment 2:
In 2000ml four neck flasks, add DMF131.6g (1.8mol), be warming up to 80 ℃, slowly add ethyl sulfate 231.3g (1.5mol), 80～90 ℃ of controlled temperature added the back insulation reaction 5 hours, and reaction is cooled to room temperature after finishing.
In flask, add orthodichlorobenzene 900ml, ethyl malonate 240.2g (1.5mol), pyridine-piperidines 59.3g～63.9g (0.75mol～0.75mol), be warming up to backflow, insulation reaction 3 hours; Reaction is cooled to 10～20 ℃ after finishing, and filters; To filtrate with after the 500ml washing three times, collected organic layer, concentrating under reduced pressure reclaims solvent, and the temperature of concentrating under reduced pressure is 70 ℃, and gauge pressure is-0.096MPa; Carry out underpressure distillation again, the temperature of underpressure distillation is 100 ℃, and vacuum tightness is more than the 5mmHg, collects the cut 184.7g of 80～85 ℃/5mmHg, is product; Content: 96.8% (HPLC).
Embodiment 3:
In 2000ml four neck flasks, add DMF131.6g (1.8mol), be warming up to 80 ℃, slowly add ethyl sulfate 231.3g (1.5mol), 80～90 ℃ of controlled temperature added the back insulation reaction 3 hours, and reaction is cooled to room temperature after finishing.
In flask, add ethylene dichloride 900ml, ethyl malonate 240.2g (1.5mol), pyridine-piperidines 59.3g～63.9g (0.75mol～0.75mol), be warming up to backflow, insulation reaction 10 hours; Reaction is cooled to room temperature after finishing, and filters; The first concentrating under reduced pressure of will filtrating reclaims solvent, and the temperature of concentrating under reduced pressure is 40 ℃, and gauge pressure is-0.09MPa; Carry out underpressure distillation again, the temperature of underpressure distillation is 98 ℃, and vacuum tightness is more than the 5mmHg, collects the cut 176.1g of 80～85 ℃/5mmHg, is product; Content: 98.3% (HPLC).
Embodiment 4:
In 2000ml four neck flasks, add DMF120.6g (1.65mol), be warming up to 80 ℃, slowly add ethyl sulfate 231.3g (1.5mol), 80～90 ℃ of controlled temperature added the back insulation reaction 2 hours, and reaction is cooled to room temperature after finishing.
In flask, add benzene 900ml, ethyl malonate 240.2g (1.5mol), pyridine 106.8g (1.35mol), be warming up to backflow, insulation reaction 8 hours; Reaction is cooled to room temperature after finishing, and filters; To filtrate with after the 500ml washing three times, collected organic layer, concentrating under reduced pressure reclaims solvent, and the temperature of concentrating under reduced pressure is 50 ℃, and gauge pressure is-0.092MPa; Carry out underpressure distillation again, the temperature of underpressure distillation is 95 ℃, and vacuum tightness is more than the 5mmHg, collects the cut 193.7g of 80～85 ℃/5mmHg, is product; Content: 98.6% (HPLC).
It is thus clear that it is raw material that technical scheme of the present invention adopts ethyl malonate, with DMF-ethyl sulfate condensation single step reaction and getting under catalyst action; Do not need isolation of intermediate products, aftertreatment technology is simple, and the yield of product and purity all are higher than the optimum value of prior art; Yield reaches as high as 90%, and product content reaches 98.5%, and quality is very good; And production cost is lower, the economic and social benefit highly significant.
Below only be concrete exemplary applications of the present invention, protection scope of the present invention is not constituted any limitation.All employing equivalents or equivalence are replaced and the technical scheme of formation, all drop within the rights protection scope of the present invention.
Claims (3)
1.3-N the preparation method of N-dimethylamino ethyl propenoate is characterized in that: may further comprise the steps---
1) (1.1～1.3) in molar ratio: 1 consumption, in DMF, add ethyl sulfate, controlled temperature is incubated 2～5 hours at 80～90 ℃, generates DMF-ethyl sulfate condensation salts solution;
2) with DMF-ethyl sulfate condensation salts solution and ethyl malonate, solvent, catalyst mix, be warming up to and reflux and reacted 3～10 hours, reduce to room temperature then; Said catalyzer is a pyridine, or pyridine-piperidines mixture;
3) reaction is cooled to 10～20 ℃ after finishing, filter, and filtrating washing back layering, collected organic layer, high vacuum underpressure distillation again behind the concentrating under reduced pressure, the cut of collecting 80～85 ℃/5mmHg is finished product; The temperature of said concentrating under reduced pressure is 40～70 ℃, gauge pressure is-0.09～-0.098MPa; The temperature of high vacuum underpressure distillation is 90～100 ℃, and vacuum tightness is 5mmHg.
2. 3-N according to claim 1; The preparation method of N-dimethylamino ethyl propenoate; It is characterized in that: step 2) in the weight ratio of ethyl malonate and DMF-ethyl sulfate condensation salts solution be 1: (1～1.3), the mol ratio of ethyl malonate and catalyzer are 1: (0.9～1.2).
3. 3-N according to claim 1 and 2, the preparation method of N-dimethylamino ethyl propenoate is characterized in that: step 2) in solvent be benzene, toluene, orthodichlorobenzene or ethylene dichloride.
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| CN2008101240242A CN101293850B (en) | 2008-06-10 | 2008-06-10 | Method for preparing 3-N,N-dimethylamino-ethyl acrylate |
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| CN2008101240242A CN101293850B (en) | 2008-06-10 | 2008-06-10 | Method for preparing 3-N,N-dimethylamino-ethyl acrylate |
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| CN101293850B true CN101293850B (en) | 2012-05-30 |
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| CN102086158B (en) * | 2009-12-31 | 2013-12-04 | 顾海宁 | Method for synthesizing 3-(N,N-2-substituted amino)-2-substituted acrylic esters |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000000460A1 (en) * | 1998-06-29 | 2000-01-06 | Sharad Kumar Vyas | Process for preparation of substituted propenoic acid esters |
| CN1257067A (en) * | 1998-11-10 | 2000-06-21 | 罗姆和哈斯公司 | Process for preparing 2-(trihalogen acetyl)-3-(substituted amino)-2-ester acrylate |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000000460A1 (en) * | 1998-06-29 | 2000-01-06 | Sharad Kumar Vyas | Process for preparation of substituted propenoic acid esters |
| CN1257067A (en) * | 1998-11-10 | 2000-06-21 | 罗姆和哈斯公司 | Process for preparing 2-(trihalogen acetyl)-3-(substituted amino)-2-ester acrylate |
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