CN114702405A - Preparation method of N-ethoxy oxalyl alanine ethyl ester - Google Patents
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- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
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- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
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- C07C231/00—Preparation of carboxylic acid amides
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Abstract
The invention provides a preparation method of N-ethoxy oxalyl alanine ethyl ester, and a large number of experiments and innovative researches find that benzene with high toxicity can be successfully replaced by a solvent with low toxicity by using absolute ethyl alcohol and toluene, and hot gas can be recycled by using a hot gas compressor, so that the energy consumption is greatly reduced, and the energy conservation and environmental protection are realized.
Description
Technical Field
The invention relates to synthesis of vitamin B6, and in particular relates to a preparation method of an N-ethoxyoxalyl alanine ethyl ester intermediate.
Background
Vitamin B6(Vitamin B6), also known as pyridoxine, includes pyridoxine, pyridoxal and pyridoxamine, exists in vivo in the form of phosphate ester, is a water-soluble Vitamin, is easily destroyed by light or alkali, and is not resistant to high temperature. Pyridoxine is thermostable, and pyridoxal and pyridoxamine are not. Vitamin B6 is marketed primarily as pyridoxine hydrochloride.
Vitamin B6 is a component of some coenzymes in human body, participates in various metabolic reactions, and especially has close relation with amino acid metabolism. The vitamin B6 preparation is clinically applied to prevent and treat vomiting of pregnancy and vomiting of radiation sickness. It can also be used for treating arteriosclerosis, alopecia, hypercholesterolemia, cystitis, hypoglycemia, mental disorder, muscular disorder, neurological disorder, emesis in early stage of pregnancy, overweight, postoperative emesis, and photosensitivity to sunlight. In recent years, vitamin B6 has been found to be useful in rescuing isoniazid poisoning, treating anemia, treating leukopenia, treating mental retardation, treating canker sore, treating arteriosclerosis and thromboembolic disease, delactation, treating Parkinson's disease, etc.
Vitamin B6 is usually produced industrially by chemical synthesis methods, mainly by the pyridone method, the oxazole method and other microbiological methods.
The pyridone method is a method for synthesizing vitamin B6 by using chloroacetic acid as a starting material and carrying out esterification, substitution, cyclization and other reactions, vitamin B6 is synthesized for the first time in 1936, and the vitamin B6 proves that the vitamin B6 has the same chemical structure and biological activity as natural extracts, and then, the research on the synthesis of vitamin B6 is actively carried out in all countries in the world, so that the rapid development of the vitamin B6 industry is promoted.
In the 60 s of the 20 th century, Firestone RA and the like use N-formyl alanine ethyl ester as an initiator to obtain a key intermediate 4-methyl-5-ethoxy oxazole through cyclization, then perform Diels-Alder reaction with dienophile, and obtain vitamin B6 through conversion treatment. This synthetic route has the advantages of readily available starting materials, high yields, etc., and this process has been referred to hereafter as the "oxazole process". The oxazole method is applied to production, so that the production cost is obviously reduced, and the sale price of the vitamin B6 is greatly reduced.
Compared with the pyridone method, the oxazole method has great progress, but has certain defects. For example, a toxic solvent benzene and strong corrosive phosphorus oxychloride are used in the synthesis process of the oxazole intermediate, and the refining process of the vitamin B6 crude product is complex.
In the oxazole process for vitamin B6, there are two important intermediate compounds: ethyl N-ethoxyoxalylalaninate and ethyl 4-methyl-5-ethoxyoxazoloate.
The preparation method of the N-ethoxyoxalyl alanine ethyl ester comprises the following steps: adding alpha-aminopropionic acid, industrial oxalic acid, hydrochloric acid, ethanol and benzene into a reaction vessel, and heating, rectifying, dehydrating and esterifying; adding diethyl oxalate and alkali into the esterification reaction liquid for reaction to prepare the N-ethoxy oxalyl alanine ethyl ester. The reaction path is as follows:
the toxic solvent benzene is used in the reaction, so that the subsequent reaction and the treatment of waste water and waste liquid are very complicated, and the health of staff is greatly damaged.
The Roche (Shanghai) vitamin Co Ltd adopts a solvent substitution technology, eliminates water-carrying agent benzene in the alanine esterification stage, and develops the first benzene-free vitamin B6 production process in China. The new benzene-free production process reduces the influence of production on the environment and improves the operation conditions, but the cost of the substitute solvent is relatively high, the process complexity is increased, and the production cost is increased.
How to avoid using toxic solvent benzene, reduce the harm to the health of staff and reduce the pollution and damage to the environment, and the realization of simple and feasible process without increasing the cost is an urgent problem to be solved.
Disclosure of Invention
The invention provides a preparation method of N-ethoxy oxalyl alanine ethyl ester, and a large number of experiments and innovative researches find that benzene with high toxicity can be successfully replaced by a solvent with low toxicity by using absolute ethyl alcohol and toluene, and steam can be recycled for the second time by using a steam compressor, so that the energy consumption is greatly reduced, and the energy conservation and environmental protection are realized.
The synthesis process adopts toluene for esterification and rectification to carry water, but due to the difference of physicochemical properties of the toluene and the benzene, the reaction time is prolonged, the energy consumption is increased, therefore, in order to reduce the production energy consumption and shorten the reaction time, the invention carries out various attempts, finally discovers that the benzene can be replaced by using absolute ethyl alcohol and the toluene, and ensures that the yield is not reduced. Through the use of the steam compressor, the steam can be recycled for the second time, so that the energy consumption is greatly reduced, and the energy conservation and environmental protection are realized. And provides a brand-new reaction system for preparing the N-ethoxyoxalyl alanine ethyl ester.
The invention provides a reaction system (or reaction equipment) of N-ethoxy oxalyl alanine ethyl ester, which comprises the following components: the device comprises a reaction container, a rectifying tower, a water separator and a vapor compressor; heating the reaction vessel so that the vapor enters the rectification column; the vapor phase enters a vapor compressor from the top of the rectifying tower, the vapor compressor increases the temperature of the vapor by compressing hot vapor, the compressed vapor is input into a reaction container, the condensed solvent enters a water separator to continuously separate a water layer, and the toluene layer is pumped into the tower by a pump.
Preferably, the reaction vessel is an esterification rectifying still.
Preferably, the reaction system further comprises a superheater, and the vapor compressor raises the temperature of the vapor by compressing the hot vapor, and then delivers the vapor to the reaction vessel through the superheater.
Preferably, the reaction system further comprises a centrifugal pump, and the vapor compressor raises the temperature of the vapor by compressing the hot vapor, and then feeds the vapor into the reaction vessel through the superheater and the centrifugal pump.
Preferably, the water separator is a delayer, and a condensation recoverer is arranged at the upper end of the delayer; the condensed solvent enters a demixer to continuously separate a water layer, and a toluene layer is pumped into the tower.
Preferably, a centrifugal pump is arranged behind the water separator, and the toluene layer is pumped into the tower after passing through the centrifugal pump.
Most preferably, the reaction system comprises: the device comprises a reaction vessel 1, a rectifying tower 2, a vapor compressor 3, a superheater 4, a centrifugal pump 5, a delayer 6, a condensation recoverer 7 and a centrifugal pump 8.
The upper end of the reaction vessel 1 is provided with a rectifying tower 2, vapor phase enters a vapor compressor 3 from the top of the rectifying tower 2, the vapor compressor 3 compresses hot vapor to increase the temperature of the vapor, and then the vapor passes through a superheater 4 and a centrifugal pump 5 and is input into the reaction vessel. The lower end of the reaction vessel 1 is provided with a delayer 6, the delayer 6 is provided with a condensation recoverer 7, condensed solvent enters the delayer 6 to continuously separate a water layer, and a toluene layer is pumped into the tower through a centrifugal pump 8.
The reaction vessel is preferably an esterification rectifying still.
The invention provides a preparation method of N-ethoxy oxalyl alanine ethyl ester, which is characterized by comprising the following steps: respectively adding 20-50 parts by mass of L-alanine, 30-80 parts by mass of oxalic acid and absolute ethyl alcohol into a mixing container, heating to 90-100 ℃ for heating and dissolving, then transferring the dissolved solution into an esterification rectifying kettle, adding 50-100 parts by mass of toluene and diethyl oxalate, heating and heating for reaction, introducing a vapor phase into a vapor compressor from the top of a rectifying tower, compressing hot vapor by the vapor compressor to increase the temperature of the vapor, inputting the compressed vapor into a reaction container, introducing the condensed solvent into a water separator to continuously separate a water layer, and pumping the toluene layer into an inflow tower through a pump; when the reaction is carried out for 20-60 hours, adding toluene and ethanol into the esterification rectifying kettle again for reaction rectification until the water separator is basically separated out and the moisture of the materials in the esterification rectifying kettle is less than 0.1 percent, and stopping the reaction; distilling toluene and ethanol at normal pressure; distilling under vacuum to remove diethyl oxalate to obtain N-ethoxy oxalyl alanine ethyl ester;
the reaction system used in the preparation method comprises: the device comprises a reaction container, a rectifying tower, a water separator and a vapor compressor; heating the reaction vessel so that steam enters the rectifying tower; the vapor phase enters a vapor compressor from the top of the rectification tower, the vapor compressor increases the temperature of the vapor by compressing hot vapor, the compressed vapor is input into a reaction container, the condensed solvent enters a water separator to continuously separate a water layer, and a toluene layer is pumped into the tower.
Preferably, the reaction vessel is an esterification rectifying still.
Preferably, the reaction system further comprises a superheater, and the vapor compressor raises the temperature of the vapor by compressing the hot vapor, and then delivers the vapor to the reaction vessel through the superheater.
Preferably, the reaction system further comprises a centrifugal pump, and the vapor compressor raises the temperature of the vapor by compressing the hot vapor, and then feeds the vapor into the reaction vessel through the superheater and the centrifugal pump.
Preferably, the water separator is a delayer, and a condensation recoverer is arranged at the upper end of the delayer; the condensed solvent enters a demixer to continuously separate a water layer, and a toluene layer is pumped into the tower.
Preferably, a centrifugal pump is arranged behind the water separator, and the toluene layer is pumped into the tower after passing through the centrifugal pump.
Most preferably, the reaction system comprises: the device comprises a reaction vessel 1, a rectifying tower 2, a vapor compressor 3, a superheater 4, a centrifugal pump 5, a delayer 6, a condensation recoverer 7 and a centrifugal pump 8.
The upper end of the reaction vessel 1 is provided with a rectifying tower 2, vapor phase enters a vapor compressor 3 from the top of the rectifying tower 2, the vapor compressor 3 compresses hot vapor to increase the temperature of the vapor, and then the vapor passes through a superheater 4 and a centrifugal pump 5 and is input into the reaction vessel. The lower end of the reaction vessel 1 is provided with a delayer 6, the delayer 6 is provided with a condensation recoverer 7, condensed solvent enters the delayer 6 to continuously separate a water layer, and a toluene layer is pumped into the tower through a centrifugal pump 8.
The reaction vessel is preferably an esterification rectifying still.
The preparation method of N-ethoxy oxalyl alanine ethyl ester is characterized by comprising the following steps: the preparation method uses a reaction system comprising: the device comprises an esterification rectifying kettle 1, a rectifying tower 2, a vapor compressor 3, a superheater 4, a centrifugal pump 5, a delayer 6, a condensation recoverer 7 and a centrifugal pump 8; a rectifying tower 2 is arranged at the upper end of an esterification rectifying kettle 1, vapor phase enters a vapor compressor 3 from the top of the rectifying tower 2, the vapor compressor 3 compresses hot vapor to increase the temperature of the vapor, and then the vapor passes through a superheater 4 and a centrifugal pump 5 and is input into a reaction container; the lower end of the esterification rectifying kettle 1 is provided with a delayer 6, the delayer 6 is provided with a condensation recoverer 7, condensed solvent enters the delayer 6 to continuously separate a water layer, and a toluene layer is pumped into the tower through a centrifugal pump 8.
The preparation method of N-ethoxy oxalyl alanine ethyl ester is characterized by comprising the following steps: respectively adding 35 parts by mass of L-alanine, 58 parts by mass of oxalic acid and absolute ethyl alcohol into a mixing container, heating to 90-100 ℃ for dissolving, transferring the dissolved solution into an esterification rectifying kettle, adding 65 parts by mass of toluene and diethyl oxalate, heating for reacting, allowing a vapor phase to enter a vapor compressor from the top of a rectifying tower, compressing hot vapor by the vapor compressor to increase the temperature of the vapor, inputting the compressed vapor into a reaction container, allowing the condensed solvent to enter a water separator for continuously separating a water layer, and pumping the toluene layer into the tower through a pump; when the reaction is carried out for 40 hours, adding toluene and ethanol into the esterification rectifying kettle again for reaction rectification until the water separator is basically separated out and the moisture of the materials in the esterification rectifying kettle is less than 0.1 percent, and stopping the reaction; evaporating toluene and ethanol at normal pressure; and (3) evaporating diethyl oxalate at 100-130 ℃/10-200 pa under vacuum and reduced pressure to obtain the N-ethoxyoxalyl alanine ethyl ester.
The preparation method of N-ethoxy oxalyl alanine ethyl ester is characterized by comprising the following steps: adding 35kg of L-alanine, 58kg of oxalic acid and 60L of absolute ethyl alcohol into a mixing container respectively, heating to 90-100 ℃ for heating and dissolving, transferring the dissolved solution into an esterification rectifying kettle, adding 50L of toluene and 65kg of diethyl oxalate, heating for reaction, introducing a vapor phase into a vapor compressor from the top of a rectifying tower, compressing hot vapor by the vapor compressor to increase the temperature of the vapor, inputting the compressed vapor into a reaction container, introducing the condensed solvent into a water separator to continuously separate a water layer, and pumping the toluene layer into the tower through a pump; when the reaction is carried out for 40 hours, adding 20 liters of toluene and 30 liters of ethanol into the esterification rectifying kettle again for reaction rectification until the water separator is basically separated out and the moisture of the materials in the esterification rectifying kettle is less than 0.1 percent, and stopping the reaction; distilling off toluene and ethanol at normal pressure; and (3) evaporating diethyl oxalate at 100-130 ℃/10-200 pa under vacuum and reduced pressure to obtain the N-ethoxyoxalyl alanine ethyl ester.
The invention realizes the successful replacement of benzene and the effects of environmental protection and energy saving.
Drawings
FIG. 1: schematic diagram of reaction system
1 is an esterification rectifying kettle 2, a rectifying tower 3, a steam compressor 4, a superheater 5, a centrifugal pump 6, a delayer 7, a condensation recoverer 8 and a centrifugal pump.
Detailed Description
Example 1:
respectively adding 35 kgL-alanine, 58kg of industrial oxalic acid and 40L of 95% ethanol into a mixing container, heating to 80 ℃ for dissolving, transferring the dissolved solution into an esterification rectifying kettle, adding 30L of benzene and 65kg of diethyl oxalate, heating for reacting, continuously separating a water layer from a water separator at the top of a rectifying tower, and allowing the benzene layer to flow into the tower. When the reaction is carried out for 40 hours, 10L of benzene and 20L of 95 percent ethanol are added into the esterification rectifying still again for reaction rectification until the water knockout drum is basically separated out and the moisture of the materials in the esterification rectifying still is less than 0.1 percent, and the reaction is stopped. Distilling off benzene and alcohol under normal pressure; and (3) evaporating diethyl oxalate at the temperature of between 100 and 130 ℃ at the speed of between 10 and 200pa under reduced pressure to obtain the N-ethoxyoxalyl alanine ethyl ester with the yield of 91 percent.
Example 2:
adding 35kg of L-alanine, 58kg of industrial oxalic acid and 40L of 95% ethanol into a mixing container respectively, heating to 80 ℃, heating to dissolve, transferring the dissolved solution into an esterification rectifying kettle, adding 30L of toluene and 65kg of diethyl oxalate, heating to raise the temperature for reaction, continuously separating a water layer from a water separator at the top of a rectifying tower, and allowing the toluene layer to flow into the tower. When the reaction is carried out for 40 hours, 10L of toluene and 20L of 95 percent ethanol are added into the esterification rectifying still again for reaction rectification until the water knockout drum is basically separated out and the moisture of the materials in the esterification rectifying still is less than 0.1 percent, and the reaction is stopped. Evaporating toluene and ethanol at normal pressure; and (3) distilling the diethyl oxalate at the temperature of between 100 and 130 ℃ and under the vacuum pressure of between 10 and 200pa to remove the diethyl oxalate to obtain the N-ethoxyoxalyl alanine ethyl ester, wherein the yield is 89 percent.
As the toxicity of toluene is much lower than that of benzene, the harm to staff and environment is small. After the solvent was replaced by toluene in example 2, the yield was found to be reduced, and the energy consumption was increased by 26% compared to example 1. Therefore, there is a need for screening methods that ensure yields and reduce energy consumption.
Example 3:
adding 35kg of L-alanine, 58kg of oxalic acid and 60L of absolute ethyl alcohol into a mixing container respectively, heating to 90-100 ℃ for heating and dissolving, transferring the dissolved solution into an esterification rectifying kettle, adding 50L of toluene and 65kg of diethyl oxalate, heating for reacting, continuously separating a water layer from a water separator at the top of a rectifying tower, and allowing the toluene layer to flow into the tower. And when the reaction is carried out for 40 hours, adding 20L of methylbenzene and 30L of ethanol into the esterification rectifying still again for reaction rectification until the water separator is basically separated out and the moisture of the material in the three-opening container is less than 0.1 percent, and stopping the reaction. Distilling off toluene and alcohol under normal pressure; and (3) evaporating diethyl oxalate at the speed of 100-130 ℃/10-200 pa in vacuum to obtain the N-ethoxyoxalyl alanine ethyl ester with the yield of 92%.
Through experiments, the yield of the reaction can be kept above 90% by using absolute ethyl alcohol and increasing the using amount of the absolute ethyl alcohol and the toluene. But the energy consumption was still increased by 33% compared to example 1.
Example 4:
adding 35kg of L-alanine, 58kg of oxalic acid and 60 liters of absolute ethyl alcohol into a mixing container respectively, heating to 90-100 ℃ for heating and dissolving, transferring the dissolved solution into an esterification rectifying kettle, adding 50L of toluene and 65kg of diethyl oxalate, heating and heating for reacting. The upper end of the esterification rectifying kettle 1 is provided with a rectifying tower 2, a vapor phase enters a vapor compressor 3 from the top of the rectifying tower 2, the vapor compressor 3 compresses hot vapor to increase the temperature of the vapor, and the vapor passes through a superheater 4 and a centrifugal pump 5 and is conveyed into a reaction container. The lower end of the esterification rectifying kettle 1 is provided with a delayer 6, the delayer 6 is provided with a condensation recoverer 7, condensed solvent enters the delayer 6 to continuously separate a water layer, and a toluene layer is pumped into the tower through a centrifugal pump 8. When the reaction is carried out for 40 hours, adding 20L of methylbenzene and 30L of ethanol into the esterification rectifying still again for reaction rectification until the water separator is basically separated out and the water content of the materials in the esterification rectifying still is less than 0.1 percent, and stopping the reaction. Distilling off toluene and alcohol under normal pressure; and (3) distilling the diethyl oxalate at the temperature of between 100 and 130 ℃ and under the vacuum pressure of between 10 and 200pa to remove the diethyl oxalate to obtain the N-ethoxyoxalyl alanine ethyl ester with the yield of 93 percent. The steam is reused by the steam compressor, so that the yield is not reduced and the energy consumption is reduced by 21% instead compared with example 1.
Therefore, it was confirmed that the production method for N-ethoxyoxalyl-alanine ethyl ester, in which benzene was replaced with toluene only, increased the yield and energy consumption. Although the yield is improved by using absolute ethyl alcohol and increasing the amount of toluene, the energy consumption is increased. Through the secondary utilization steam, the secondary steam generated by the rectifying tower enters the steam compressor to be compressed, the steam heat value is improved, and the energy consumption is greatly reduced. Therefore, by combined use, the benzene is successfully replaced by the toluene with lower toxicity, the energy consumption is reduced, and the energy conservation and environmental protection are realized.
The foregoing description is a general description of the invention. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation, as form changes and equivalents may be employed. Various changes or modifications may be effected therein by one skilled in the art and equivalents may be made thereto without departing from the scope of the invention as defined in the claims appended hereto.
Claims (3)
1. A preparation method of N-ethoxy oxalyl alanine ethyl ester is characterized by comprising the following steps: respectively adding 20-50 parts by mass of L-alanine, 30-80 parts by mass of oxalic acid and absolute ethyl alcohol into a mixing container, heating to 90-100 ℃ for dissolving, transferring the dissolved solution into an esterification rectifying kettle, adding 50-100 parts by mass of toluene and diethyl oxalate, heating for reacting, introducing a vapor phase into a vapor compressor from the top of a rectifying tower, compressing hot vapor by the vapor compressor to increase the temperature of the vapor, inputting the compressed vapor into a reaction container, introducing the condensed solvent into a water separator to continuously separate a water layer, and pumping the toluene layer into the tower through a pump; when the reaction is carried out for 20-60 hours, adding toluene and ethanol into the esterification rectifying still again for reaction rectification until the water separator is basically separated out and the moisture of the materials in the esterification rectifying tower is less than 0.1 percent, and stopping the reaction; evaporating toluene and ethanol at normal pressure; distilling under vacuum to remove diethyl oxalate to obtain N-ethoxy oxalyl alanine ethyl ester;
the reaction system used in the preparation method comprises: the device comprises an esterification rectifying kettle (1), a rectifying tower (2), a vapor compressor (3), a superheater (4), a centrifugal pump (5), a delayer (6), a condensation recoverer (7) and a centrifugal pump (8);
a rectifying tower (2) is arranged at the upper end of the esterification rectifying kettle (1), a vapor phase enters a vapor compressor (3) from the top of the rectifying tower (2), the vapor compressor (3) compresses hot vapor to raise the temperature of the vapor, and then the vapor passes through a superheater (4) and a centrifugal pump (5) and is input into a reaction container; the lower end of the esterification rectifying kettle (1) is provided with a delayer (6), the delayer (6) is provided with a condensation recoverer (7), a condensed solvent enters the delayer (6) to continuously separate a water layer, and a toluene layer is pumped into the tower through a centrifugal pump (8).
2. The process for the preparation of ethyl N-ethoxyoxalyl-alaninate according to claim 1, characterized in that: respectively adding 35 parts by mass of L-alanine, 58 parts by mass of oxalic acid and absolute ethyl alcohol into a mixing container, heating to 90-100 ℃ for heating and dissolving, transferring the dissolved solution into an esterification rectifying kettle, adding 65 parts by mass of toluene and diethyl oxalate, heating and heating for reaction, enabling a vapor phase to enter a vapor compressor from the top of a rectifying tower, compressing hot vapor by the vapor compressor to increase the temperature of the vapor, inputting the compressed vapor into a reaction container, enabling the condensed solvent to enter a water separator for continuously separating a water layer, pumping the toluene layer into the tower through a pump, adding toluene and ethanol into the esterification rectifying kettle again for reaction and rectification when the reaction is carried out for 40 hours, and stopping the reaction until the water separator is basically separated out and the moisture of the materials in the esterification rectifying kettle is less than 0.1%; evaporating toluene and ethanol at normal pressure; and (3) evaporating diethyl oxalate at the temperature of between 100 and 130 ℃ at the speed of between 10 and 200pa in vacuum and reducing pressure to obtain the N-ethoxy oxalyl alanine ethyl ester.
3. The process for the preparation of ethyl N-ethoxyoxalyl-alaninate according to claim 1, characterized in that: respectively adding 35 kgL-alanine, 58kg oxalic acid and 60L absolute ethyl alcohol into a mixing container, heating to 90-100 ℃ for heating and dissolving, transferring the dissolved solution into an esterification rectifying kettle, adding 50L toluene and 65kg diethyl oxalate, heating and heating for reacting, feeding a vapor phase into a vapor compressor from the top of a rectifying tower, compressing hot vapor by the vapor compressor to increase the temperature of the vapor, inputting the compressed vapor into a reaction container, feeding the condensed solvent into a water separator to continuously separate a water layer, and pumping the toluene layer into the tower through a pump; when the reaction is carried out for 40 hours, adding 20L of methylbenzene and 30L of ethanol into the esterification rectifying kettle again for reaction rectification until the water separator is basically separated out and the moisture of the materials in the esterification rectifying kettle is less than 0.1 percent, and stopping the reaction; evaporating toluene and ethanol at normal pressure; and (3) evaporating diethyl oxalate at the temperature of between 100 and 130 ℃ at the speed of between 10 and 200pa in vacuum and reducing pressure to obtain the N-ethoxy oxalyl alanine ethyl ester.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN85109641A (en) * | 1984-10-19 | 1986-06-10 | 武田药品工业株式会社 | Carry out the method and the device thereof of chemical dehydration reaction |
| WO2004087640A1 (en) * | 2003-04-04 | 2004-10-14 | Dsm Ip Assets B.V. | Process for the manufacture of n-alkoxalyl-alaninates |
| CN101830821A (en) * | 2010-05-12 | 2010-09-15 | 浙江工业大学 | Chemical synthesis method of N-alcoxyloxalyl alanine ester |
| CN104725262A (en) * | 2013-12-23 | 2015-06-24 | 大丰海嘉诺药业有限公司 | Method for continuously preparing N-ethyloxyl oxalyl alanine ethyl ester |
-
2022
- 2022-04-25 CN CN202210447904.3A patent/CN114702405A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN85109641A (en) * | 1984-10-19 | 1986-06-10 | 武田药品工业株式会社 | Carry out the method and the device thereof of chemical dehydration reaction |
| WO2004087640A1 (en) * | 2003-04-04 | 2004-10-14 | Dsm Ip Assets B.V. | Process for the manufacture of n-alkoxalyl-alaninates |
| CN101830821A (en) * | 2010-05-12 | 2010-09-15 | 浙江工业大学 | Chemical synthesis method of N-alcoxyloxalyl alanine ester |
| CN104725262A (en) * | 2013-12-23 | 2015-06-24 | 大丰海嘉诺药业有限公司 | Method for continuously preparing N-ethyloxyl oxalyl alanine ethyl ester |
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