A process for the recovery of 5-(n-ethyl-n-hydroxyethyl)-2-aminopentane

Abstract

The application discloses a method for recycling 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane, which comprises the following steps: 1) adjusting the pH value of wastewater to 12-14 to obtain a first mixed solution; 2) adding an organic solvent to the first mixed solution for extraction to obtain an organic phase containing 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane; 3) performing vacuum concentration on the organic phase to obtain a concentrated solution; and 4) performing vacuum distillation on the concentrated solution, heating to 195-210 DEG C, and collecting a fraction at 190-200 DEG C to obtain 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane, wherein the wastewater is generated in the post-treatment stage of an amination reaction of hydroxychloroquine synthesis, and the organic solvent is at least one selected from dichloromethane, toluene and ethyl acetate. Thus, 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane in the wastewater can be recycled, the purity of the recycled substance reaches 98% or above, the recycled 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane can be reused, and a large amount of production cost can be saved.

Description

TECHNICAL FIELD

[0001] The present application relates to the chemical industry field, in particular, to a method for recycling 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane. BACKGROUND

[0002] In the synthesis process of hydroxychloroquine sulfate, 4,7-dichloroquinoline and side chain are used as starting materials, and the amination reaction is carried out in the presence of phenol and potassium iodide. After the reaction is completed, acidification, alkalization, separation of the organic phase, addition of an organic solvent to the obtained organic phase, cooling and crystallization, and filtration of the hydroxychloroquinoline crude product, then purification to obtain hydroxychloroquine refined product, and finally salification with sulfuric acid to obtain hydroxychloroquine sulfate finished product. In order to improve the yield of hydroxychloroquine sulfate, one of the raw materials, 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane, needs to be fed in excess to ensure more complete reaction. Therefore, there is a lot of 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane remaining in the wastewater after the amination reaction of hydroxychloroquine sulfate synthesis (the aqueous phase discarded after acidification, alkalization and extraction after the reaction is completed). The existing process generally adopts the direct discharge method, which will cause industrial pollution and increase the difficulty of industrial water treatment. In addition, 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane is relatively expensive, and excessive feeding without recycling will cause waste of raw materials and increase production costs.

[0003] Therefore, it is urgent to find a method for recycling 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane from the wastewater after the amination reaction treatment stage of hydroxychloroquine sulfate synthesis, so as to realize the recycling of 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane. Not only can it save production costs, but also can reduce environmental pressure. SUMMARY

[0004] The present application aims to alleviate or solve at least one of the above-mentioned problems to at least some extent. After analysis, the impurities in the wastewater include phenol, 5-chloro-2-pentanone, N-ethyl ethanolamine and inorganic salts. In view of this, one object of the present application is to provide a method for recycling 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane from wastewater, so as to recycle it.

[0005] In one aspect of the present application, the present application provides a method for recycling 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane, characterized in that it comprises: 1) adjusting the pH value of wastewater to 12-14 to obtain a first mixed solution; 2) adding an organic solvent to the first mixed solution for extraction to obtain an organic phase containing 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane; 3) concentrating the organic phase under reduced pressure to obtain a concentrated solution; and 4) distilling the concentrated solution under reduced pressure, and collecting a fraction at 190-200 DEG C by heating to 195-210 DEG C to obtain 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane, wherein the wastewater is generated from the post-treatment of the ammination reaction of hydroxychloroquine sulfate synthesis; and the organic solvent is selected from at least one of dichloromethane, toluene and ethyl acetate. Thus, 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane in the wastewater can be recycled, and the purity of the recycled material reaches 98% or more, the recycled 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane can be reused, and a large amount of production cost can be saved; and the subsequent treatment of the wastewater is facilitated, the environmental pressure is reduced, and the environmental pollution caused by the discharge of wastewater containing a large amount of 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane is avoided.

[0006] According to an embodiment of the present application, the concentrated solution is distilled under reduced pressure at a vacuum degree of about -0.085 MPa.

[0007] According to an embodiment of the present application, in step 3), the temperature for concentrating the organic phase under reduced pressure is 30-110 DEG C.

[0008] According to an embodiment of the present application, the solvent is dichloromethane, toluene or ethyl acetate.

[0009] According to an embodiment of the present application, the organic solvent is dichloromethane.

[0010] According to an embodiment of the present application, in step 3), the temperature for concentrating the organic phase under reduced pressure is 30-60 DEG C.

[0011] According to an embodiment of the present application, the organic solvent is toluene.

[0012] According to an embodiment of the present application, in step 3), the temperature for concentrating the organic phase under reduced pressure is 70-110 DEG C.

[0013] According to an embodiment of the present application, the organic solvent is ethyl acetate.

[0014] According to an embodiment of the present application, in step 3), the temperature for concentrating the organic phase under reduced pressure is 50-80 DEG C.

[0015] According to an embodiment of the present application, in step 3), further comprising: recovering the organic solvent after the organic phase is concentrated under reduced pressure.

[0016] According to an embodiment of the present application, in step 2), the extraction comprises multiple extractions, and the multiple extracted organic phases are combined to obtain the organic phase containing 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane. BRIEF DESCRIPTION OF DRAWINGS

[0017] The above and / or additional aspects and advantages of the present application will become apparent and more readily appreciated from the following description, taken in conjunction with the following drawings in which:

[0018] Figure 1 The purity test results of the recovered product according to Example 1 of the present application are shown;

[0019] Figure 2 The purity test results of the recovered product according to Example 2 of the present application are shown;

[0020] Figure 3 The purity test results of the recovered product according to Example 3 of the present application are shown;

[0021] Figure 4 The purity test results of the recovered product according to Example 4 of the present application are shown;

[0022] Figure 5 The purity test results of the recovered product according to Example 5 of the present application are shown;

[0023] Figure 6 The purity test results of the recovered product according to Example 6 of the present application are shown;

[0024] Figure 7 The purity test results of the recovered product according to Example 7 of the present application are shown;

[0025] Figure 8 The purity test results of the recovered product according to Example 8 of the present application are shown;

[0026] Figure 9 The purity test results of the recovered product according to Comparative Example 1 of the present application are shown;

[0027] Figure 10 The purity test results of the recovered product according to Comparative Example 2 of the present application are shown. DETAILED DESCRIPTION

[0028] Embodiments of the present invention are described in detail below. Examples of these embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present invention, and should not be construed as limiting the present invention.

[0029] As mentioned earlier, in the synthesis process of hydroxychloroquine, excessive feeding of 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane, one of the raw materials, results in a large amount of 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane residue in the post-treatment waste liquid. Direct discharge of this residue will cause industrial pollution. Furthermore, excessive feeding without recycling will lead to waste of raw materials and increased production costs.

[0030] To at least partially alleviate or resolve the above problems, in one aspect of the present invention, a method for recovering 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane is proposed, the method comprising the following steps:

[0031] 1) Adjust the pH of the wastewater to 12-14 to obtain the first mixed liquid;

[0032] 2) Add an organic solvent to the first mixture for extraction to obtain an organic phase containing 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane;

[0033] 3) The organic phase is concentrated under reduced pressure to obtain a concentrated solution;

[0034] 4) Distill the concentrated liquid under reduced pressure, heat it to 195-210℃, and collect the fraction at 190-200℃ to obtain 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane.

[0035] In step 1), an alkali is added to the wastewater to adjust the pH to 12-14, resulting in a first mixture. The alkali added to the wastewater can be caustic soda flakes (solid sodium hydroxide) or an aqueous solution of sodium hydroxide (the concentration of sodium hydroxide can be set according to actual needs). Furthermore, the process of adding the alkali to the wastewater can be carried out under stirring conditions to ensure uniform mixing of the alkali and wastewater. According to an embodiment of the present invention, the aforementioned wastewater can be wastewater generated from the post-treatment stage of the amination reaction of hydroxychloroquine.

[0036] In step 2), after the pH of the wastewater is adjusted to 12-14, the organic solvent is added to the first mixed solution, stirring is performed, and then extraction is performed. Specifically, standing and separation can be performed to obtain an organic phase containing 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane. The extraction can further include multiple extractions. Specifically, the aqueous phase can be extracted with the organic solvent again, and the organic phases obtained by multiple extractions are combined to obtain the organic phase containing 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane.

[0037] According to embodiments of the present application, the organic solvent can be selected from at least one of dichloromethane, toluene, and ethyl acetate. That is, the organic solvent can be one of the above-mentioned organic substances or a combination of multiple substances. According to some embodiments of the present application, the organic solvent can be dichloromethane. The solubility of 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane in dichloromethane is high, and dichloromethane and solvent water in the wastewater are immiscible. Therefore, the 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane in the wastewater can be dissolved in dichloromethane by extraction, and separated from the aqueous phase by liquid separation to obtain the organic phase containing 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane. According to other embodiments of the present application, the organic solvent can be toluene. The solubility of 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane in toluene is also high, and toluene and water are immiscible. Therefore, the 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane in the wastewater can also be dissolved in toluene by extraction, and separated from the aqueous phase by liquid separation to obtain the organic phase containing 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane. According to still other embodiments of the present application, the organic solvent can be ethyl acetate. The solubility of 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane in ethyl acetate is also high, and ethyl acetate and water are immiscible. Therefore, the 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane in the wastewater can be dissolved in ethyl acetate by extraction, and separated from the aqueous phase by liquid separation to obtain the organic phase containing 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane.

[0038] According to embodiments of the present application, after the organic solvent is added to the first mixed solution, stirring can be performed for 10-15 min, for example, for 10 min, 11 min, 12 min, 13 min, 14 min, 15 min, etc. In this way, the 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane in the wastewater can be fully contacted with the organic solvent, so that the 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane is dissolved in the organic solvent, which is conducive to subsequent separation of the 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane from the aqueous phase by extraction, and further conducive to increasing the recovery amount of the 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane.

[0039] According to some embodiments of the present application, after the stirring, extraction is performed, and static separation is performed. According to some embodiments of the present application, multiple extractions can be performed to sufficiently recover 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane in the waste liquid. In addition, according to other embodiments of the present application, after multiple extractions, the organic phases can be combined, and subsequent organic solvent recovery and collection of the final product can be performed. According to embodiments of the present application, in the static separation step, the time for static separation is greater than 30 min, for example, can be 35 min, 40 min, 50 min, 1 h, 2 h, etc., so that the aqueous phase and the organic phase are sufficiently separated.

[0040] In step 3), the organic phase is concentrated under reduced pressure to obtain a concentrated liquid. According to some embodiments of the present application, after obtaining the organic phase containing 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane, the organic phase is concentrated under reduced pressure to obtain a concentrated liquid. According to other embodiments of the present application, the organic phases obtained by multiple extractions can be combined, and then concentrated under reduced pressure to obtain a concentrated liquid.

[0041] According to some embodiments of the present application, in step 3), further comprising: recovering the organic solvent after the organic phase is concentrated under reduced pressure. According to some specific embodiments of the present application, the organic solvent can be distilled out at a relatively low temperature, and the organic solvent can be used multiple times.

[0042] According to some specific embodiments of the present application, in step 3), the temperature for concentrating the organic phase under reduced pressure can be 30-110°C, for example, can be 30°C, 40°C, 50°C, 60°C, 70°C, 80°C, 90°C, 100°C, 110°C, etc. At the above temperature, the organic solvent can be distilled out for subsequent multiple uses.

[0043] It should be noted that in step 3), the distillation temperature for distilling out the organic solvent is related to the type of the organic solvent. According to some embodiments of the present application, when ethyl acetate is used as the organic solvent, a distillation temperature of 50-80°C can be used for distillation. Within this temperature range, ethyl acetate can be separated from the organic phase. According to other embodiments of the present application, when dichloromethane is used as the organic solvent, a distillation temperature of 30-60°C can be used for distillation. Within this temperature range, dichloromethane can be separated from the organic phase. According to still other embodiments of the present application, when toluene is used as the organic solvent, a distillation temperature of 70-110°C can be used for distillation. Within this temperature range, toluene can be separated from the organic phase.

[0044] In step 4), the concentrated solution is distilled under reduced pressure at a vacuum degree of about -0.085 MPa, and after distilling off the organic solvent, the temperature is continuously increased until 195-210°C after observing that substantially no droplets appear, so that the concentrated solution is boiled, and a fraction of 190-200°C is collected to obtain 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane.

[0045] After observing that substantially no droplets appear, it is indicated that the organic solvent has been substantially distilled off, and the organic phase is substantially free of the added organic solvent, and then the temperature is continuously increased until 195-210°C, so that the concentrated solution is boiled, and a fraction of 190-200°C is collected to obtain 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane, and the purity of the product is higher than 98%, and the purity of 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane is higher than that of a fraction at other temperatures.

[0046] According to an embodiment of the present application, the product obtained by the recycling method of the present application can be subjected to purity detection by gas chromatography, and the specific conditions are as follows:

[0047] Sample preparation: 1.0 ml of the product is measured and placed in a 10-ml volumetric flask, diluted to the mark with methanol, and uniformly mixed.

[0048] The chromatographic conditions are as follows:

[0049] Chromatographic column: capillary column DB-624 (30 m x 0.32 mm x 0.25 μm)

[0050] Detector: FID (flame ionization detector)

[0051] Temperature: column temperature 170°C, vaporization temperature 250°C, detector temperature 250°C

[0052] Gas flow rate: column flow rate (nitrogen), 1.00 ml / min; hydrogen, 55 kPa (about 40 ml / min); air, 40 kPa (about 400 ml / min)

[0053] Split ratio: 1:100

[0054] Purge flow rate: 3.0 ml / min

[0055] Additional flow control: AMC.R (30.0 ml / min)

[0056] Injection volume: 0.5 μl

[0057] Collection time: run to 2 times the retention time of the main peak.

[0058] In addition, according to the embodiments of the present application, the product obtained by the recycling method of the present application can be subjected to moisture determination by a moisture meter, and the specific conditions are as follows:

[0059] Reagents and solutions: Fehling's solution, anhydrous methanol

[0060] Instrument equipment: moisture meter, analytical balance

[0061] Analysis steps: take 1.0 g of the product, and determine the moisture content according to the moisture determination method (general rule 0832 first method), and the moisture content should not be more than 0.5%.

[0062] The calculation formula is as follows:

[0063]

[0064] V: the volume of Fehling's solution consumed by the test sample, in ml;

[0065] F: the mass of water corresponding to 1 ml of Fehling's solution, in mg / ml;

[0066] m: the mass of the test sample, in g.

[0067] In general, the method provided by the present application can be used to treat the wastewater generated in the amine reaction post-processing stage of hydroxychloroquine synthesis, and high-purity 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane product can be recovered, which can be reused, reducing production costs, and avoiding pollution caused by direct discharge of wastewater to the environment.

[0068] The present application will be described below through specific examples, and those skilled in the art can understand that the specific examples below are only for illustrative purposes, and do not limit the scope of the present application in any way. If the specific techniques or conditions are not specified in the examples, they are performed according to the techniques or conditions described in the literature in the art or according to the product instructions. If the reagents or instruments used are not specified by the manufacturer, they are all conventional products that can be obtained commercially.

[0069] It should be noted that the volume of wastewater to be treated in the following examples 1-8 and comparative examples 1-11 is 1 L, but the method provided by the present application can also be applied to the recovery of 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane from wastewater with a larger volume, for example, the method of the present application can be used in industrial applications to recover and reuse 5-(N-ethyl-N-hydroxyethyl)-2-amino pentane from wastewater generated in the amine reaction post-processing stage of hydroxychloroquine synthesis, thereby saving the production cost of the enterprise.

[0070] Example 1

[0071] To the container, add the wastewater from the post-treatment stage of the synthesis process of hydroxychloroquine, start stirring, add liquid alkali to adjust the pH to 14, add dichloromethane extraction, the amount of dichloromethane added is 10% of the volume of the wastewater, stir for 10-15 min, and stand for more than 30 min. Separate the liquid, re-extract the aqueous phase with 5% of the volume of the wastewater dichloromethane, combine the organic phase, and reduce pressure to concentrate to obtain a concentrated liquid. Distill the concentrated liquid under reduced pressure at a vacuum degree of about -0.085 MPa, first heat to 30-60°C, and recover dichloromethane (dichloromethane can be used multiple times). After basically no liquid droplets appear, continue to heat to 195-210°C, make the mixture boil, and collect the 190-200°C fraction. Each liter of wastewater can recover 93.2 g of product, and the appearance of the product is colorless and transparent.

[0072] Example 2

[0073] To the container, add the wastewater from the post-treatment stage of the synthesis process of hydroxychloroquine, start stirring, add liquid alkali to adjust the pH to 14, add dichloromethane extraction, the amount of dichloromethane added is 10% of the volume of the wastewater, stir for 10-15 min, and stand for more than 30 min. Separate the liquid, re-extract the aqueous phase with 5% of the volume of the wastewater dichloromethane, combine the organic phase, and reduce pressure to concentrate to obtain a concentrated liquid. Distill the concentrated liquid under reduced pressure at a vacuum degree of about -0.085 MPa, first heat to 30-60°C, and recover dichloromethane (dichloromethane can be used multiple times). After basically no liquid droplets appear, continue to heat to 195-210°C, make the mixture boil, and collect the 190-200°C fraction. Each liter of wastewater can recover 93.2 g of product, and the appearance of the product is colorless and transparent.

[0074] Example 3

[0075] To the container, add the wastewater from the post-treatment stage of the synthesis process of hydroxychloroquine, start stirring, add liquid alkali to adjust the pH to 14, add dichloromethane extraction, the amount of dichloromethane added is 10% of the volume of the wastewater, stir for 10-15 min, and stand for more than 30 min. Separate the liquid, re-extract the aqueous phase with 5% of the volume of the wastewater dichloromethane, combine the organic phase, and reduce pressure to concentrate to obtain a concentrated liquid. Distill the concentrated liquid under reduced pressure at a vacuum degree of about -0.085 MPa, first heat to 30-60°C, and recover dichloromethane (dichloromethane can be used multiple times). After basically no liquid droplets appear, continue to heat to 195-210°C, make the mixture boil, and collect the 190-200°C fraction. Each liter of wastewater can recover 93.2 g of product, and the appearance of the product is colorless and transparent.

[0076] Example 4

[0077] To the container, add the wastewater from the post-treatment stage of the synthesis process of hydroxychloroquine, start stirring, add liquid alkali to adjust the pH to 12, add dichloromethane for extraction, the amount of dichloromethane added is 10% of the volume of the wastewater, stir for 10-15 min, and stand for more than 30 min. Separate the liquid, re-extract the aqueous phase with 5% of the volume of the wastewater of dichloromethane, combine the organic phases, and concentrate under reduced pressure to obtain a concentrated liquid. Distill the concentrated liquid under reduced pressure at a vacuum degree of about -0.085 MPa, first heat to 30-60°C, and recover dichloromethane (dichloromethane can be used multiple times). After basically no liquid droplets appear, continue to heat to 195-210°C, make the mixture boil, and collect the fraction at 190-200°C. Each liter of wastewater can recover 83.1 g of product, and the appearance of the product is colorless and transparent.

[0078] Example 5

[0079] To the container, add the wastewater from the post-treatment stage of the synthesis process of hydroxychloroquine, start stirring, add liquid alkali to adjust the pH to 12, add dichloromethane for extraction, the amount of dichloromethane added is 10% of the volume of the wastewater, stir for 10-15 min, and stand for more than 30 min. Separate the liquid, re-extract the aqueous phase with 5% of the volume of the wastewater of dichloromethane, combine the organic phases, and concentrate under reduced pressure to obtain a concentrated liquid. Distill the concentrated liquid under reduced pressure at a vacuum degree of about -0.085 MPa, first heat to 30-60°C, and recover dichloromethane (dichloromethane can be used multiple times). After basically no liquid droplets appear, continue to heat to 195-210°C, make the mixture boil, and collect the fraction at 190-200°C. Each liter of wastewater can recover 83.1 g of product, and the appearance of the product is colorless and transparent.

[0080] Example 6

[0081] To the container, add the wastewater from the post-treatment stage of the synthesis process of hydroxychloroquine, start stirring, add liquid alkali to adjust the pH to 12, add dichloromethane for extraction, the amount of dichloromethane added is 10% of the volume of the wastewater, stir for 10-15 min, and stand for more than 30 min. Separate the liquid, re-extract the aqueous phase with 5% of the volume of the wastewater of dichloromethane, combine the organic phases, and concentrate under reduced pressure to obtain a concentrated liquid. Distill the concentrated liquid under reduced pressure at a vacuum degree of about -0.085 MPa, first heat to 30-60°C, and recover dichloromethane (dichloromethane can be used multiple times). After basically no liquid droplets appear, continue to heat to 195-210°C, make the mixture boil, and collect the fraction at 190-200°C. Each liter of wastewater can recover 83.1 g of product, and the appearance of the product is colorless and transparent.

[0082] Example 7

[0083] To the container, add the wastewater from the post-treatment stage of the synthesis process of hydroxychloroquine, start stirring, add liquid alkali to adjust the pH to 14, add dichloromethane for extraction, the amount of dichloromethane added is 5% of the volume of the wastewater, stir for 10-15 min, and stand for more than 30 min. Separate the liquid, re-extract the aqueous phase with 5% of the volume of the wastewater of dichloromethane, combine the organic phases, and concentrate under reduced pressure to obtain a concentrated liquid. Distill the concentrated liquid under reduced pressure at a vacuum degree of about -0.085 MPa, first heat to 30-60°C, recover the dichloromethane (which can be used multiple times). After basically no liquid droplets appear, continue to heat to 195-210°C, make the mixture boil, collect the fraction at 190-200°C, and recover 92.4 g of product per liter of wastewater. The appearance of the product is colorless and transparent.

[0084] Example 8

[0085] To the container, add the wastewater from the post-treatment stage of the synthesis process of hydroxychloroquine, start stirring, add liquid alkali to adjust the pH to 14, add dichloromethane for extraction, the amount of dichloromethane added is 5% of the volume of the wastewater, stir for 10-15 min, and stand for more than 30 min. Separate the liquid, re-extract the aqueous phase with 5% of the volume of the wastewater of dichloromethane, combine the organic phases, and concentrate under reduced pressure to obtain a concentrated liquid. Distill the concentrated liquid under reduced pressure at a vacuum degree of about -0.085 MPa, first heat to 30-60°C, recover the dichloromethane (which can be used multiple times). After basically no liquid droplets appear, continue to heat to 195-210°C, make the mixture boil, collect the fraction at 190-200°C, and recover 92.4 g of product per liter of wastewater. The appearance of the product is colorless and transparent.

[0086] Comparative Example 1

[0087] To the container, add the wastewater from the post-treatment stage of the synthesis process of hydroxychloroquine, start stirring, add liquid alkali to adjust the pH to 14, add dichloromethane for extraction, the amount of dichloromethane added is 5% of the volume of the wastewater, stir for 10-15 min, and stand for more than 30 min. Separate the liquid, re-extract the aqueous phase with 5% of the volume of the wastewater of dichloromethane, combine the organic phases, and concentrate under reduced pressure to obtain a concentrated liquid. Distill the concentrated liquid under reduced pressure at a vacuum degree of about -0.085 MPa, first heat to 30-60°C, recover the dichloromethane (which can be used multiple times). After basically no liquid droplets appear, continue to heat to 195-210°C, make the mixture boil, collect the fraction at 190-200°C, and recover 92.4 g of product per liter of wastewater. The appearance of the product is colorless and transparent.

[0088] Comparative Example 2

[0089] The wastewater from the production of hydroxyl chloroquine amine synthesis process post-treatment stage was added into the container, the stirring was started, the liquid alkali was added to adjust the pH to 10, the dichloromethane was added for extraction, the amount of dichloromethane added was 10% of the volume of the wastewater, the stirring was performed for 10-15 min, and the standing was performed for more than 30 min. The liquid separation was performed, the water phase was extracted again with 5% of the volume of the wastewater of dichloromethane, the organic phases were combined, and the concentrated liquid was obtained by reducing pressure concentration. The concentrated liquid was distilled under reduced pressure at a vacuum degree of about -0.085 MPa, the temperature was first increased to 30-60°C, and the dichloromethane (the dichloromethane could be used repeatedly) was recovered. After basically no liquid drops appeared, the temperature was continuously increased to 195-210°C, the mixture was boiled, and the fraction of 190-200°C was collected. The product of 54.1 g could be recovered per liter of wastewater, and the product was colorless and transparent.

[0090] Comparative Example 3

[0091] 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane was recovered according to the same method as in Example 5, except that the liquid alkali was added to adjust the pH to 8. The product of 25.5 g was obtained by this method, and the product was colorless and transparent.

[0092] Comparative Example 4

[0093] 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane was recovered according to the same method as in Example 4, except that the liquid alkali was added to adjust the pH to 8. The product of 28.5 g was obtained by this method, and the product was colorless and transparent.

[0094] Comparative Example 5

[0095] 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane was recovered according to the same method as in Example 5, except that the liquid alkali was added to adjust the pH to 9. The product of 33.5 g was obtained by this method, and the product was colorless and transparent.

[0096] Comparative Example 6

[0097] 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane was recovered according to the same method as in Example 4, except that the liquid alkali was added to adjust the pH to 9. The product of 38.4 g was obtained by this method, and the product was colorless and transparent.

[0098] Comparative Example 7

[0099] To the container was added the wastewater from the post-treatment stage of the synthesis of hydroxychloroquine production process, the stirring was started, liquid alkali was added to adjust the pH to 14, n-hexane was added for extraction, the amount of n-hexane added was 10% of the volume of the wastewater, stirring was performed for 10-15 min, and the mixture was allowed to stand for more than 30 min. The liquid was separated, the aqueous phase was again extracted with 5% of the volume of the wastewater of n-hexane, the organic phases were combined, and the concentrated liquid was obtained by concentration under reduced pressure. The concentrated liquid was distilled under reduced pressure at a vacuum degree of about -0.085 MPa, the temperature was first raised to 60-80°C, and n-hexane was recovered (n-hexane can be used repeatedly). After the appearance of substantially no liquid droplets, the temperature was continuously raised to 195-210°C, the mixture was boiled, and the fraction of 190-200°C was collected. The product of 74.2 g was recovered per liter of wastewater, and the product was colorless and transparent.

[0100] Comparative Example 8

[0101] To the container was added the wastewater from the post-treatment stage of the synthesis of hydroxychloroquine production process, the stirring was started, liquid alkali was added to adjust the pH to 14, n-hexane was added for extraction, the amount of n-hexane added was 10% of the volume of the wastewater, stirring was performed for 10-15 min, and the mixture was allowed to stand for more than 30 min. The liquid was separated, the aqueous phase was again extracted with 5% of the volume of the wastewater of n-hexane, the organic phases were combined, and the concentrated liquid was obtained by concentration under reduced pressure. The concentrated liquid was distilled under reduced pressure at a vacuum degree of about -0.085 MPa, the temperature was first raised to 60-80°C, and n-hexane was recovered (n-hexane can be used repeatedly). After the appearance of substantially no liquid droplets, the temperature was continuously raised to 195-210°C, the mixture was boiled, and the fraction of 190-200°C was collected. The product of 74.2 g was recovered per liter of wastewater, and the product was colorless and transparent.

[0102] Comparative Example 9

[0103] To the container was added the wastewater from the post-treatment stage of the synthesis of hydroxychloroquine production process, the stirring was started, liquid alkali was added to adjust the pH to 14, n-hexane was added for extraction, the amount of n-hexane added was 10% of the volume of the wastewater, stirring was performed for 10-15 min, and the mixture was allowed to stand for more than 30 min. The liquid was separated, the aqueous phase was again extracted with 5% of the volume of the wastewater of n-hexane, the organic phases were combined, and the concentrated liquid was obtained by concentration under reduced pressure. The concentrated liquid was distilled under reduced pressure at a vacuum degree of about -0.085 MPa, the temperature was first raised to 60-80°C, and n-hexane was recovered (n-hexane can be used repeatedly). After the appearance of substantially no liquid droplets, the temperature was continuously raised to 195-210°C, the mixture was boiled, and the fraction of 190-200°C was collected. The product of 74.2 g was recovered per liter of wastewater, and the product was colorless and transparent.

[0104] Comparative Example 10

[0105] The wastewater from the post-treatment stage of the synthesis of hydroxychloroquine amine is added to a container, stirring is started, liquid alkali is added to adjust the pH to 14, toluene is added for extraction, the amount of toluene added is 10% of the volume of the wastewater, stirring is carried out for 10-15 minutes, and the mixture is allowed to stand for more than 30 minutes. The liquid is separated, the aqueous phase is extracted again with 5% of the volume of the wastewater of toluene, the organic phases are combined, and the concentrated liquid is obtained by concentration under reduced pressure. The concentrated liquid is distilled under reduced pressure at a vacuum degree of about -0.085 MPa, the temperature is first raised to 70-110°C, and toluene is recovered (the toluene can be used repeatedly). After basically no liquid droplets appear, the temperature is continuously raised, and the fraction at 160-190°C is collected. The product of 18.8 g can be recovered per liter of wastewater.

[0106] Comparative Example 11

[0107] The wastewater from the post-treatment stage of the synthesis of hydroxychloroquine amine is added to a container, stirring is started, liquid alkali is added to adjust the pH to 14, toluene is added for extraction, the amount of toluene added is 10% of the volume of the wastewater, stirring is carried out for 10-15 minutes, and the mixture is allowed to stand for more than 30 minutes. The liquid is separated, the aqueous phase is extracted again with 5% of the volume of the wastewater of toluene, the organic phases are combined, and the concentrated liquid is obtained by concentration under reduced pressure. The concentrated liquid is distilled under reduced pressure at a vacuum degree of about -0.085 MPa, the temperature is first raised to 70-110°C, and toluene is recovered (the toluene can be used repeatedly). After basically no liquid droplets appear, the temperature is continuously raised, and the fraction at 160-190°C is collected. The product of 18.8 g can be recovered per liter of wastewater.

[0108] The purity of the products obtained in Examples 1-8 and Comparative Examples 1-11 is determined by the gas chromatography method described above, and the determination results of Examples 1-8 and Comparative Examples 1-2 are shown in Table 1 below. The gas chromatograms of Comparative Examples 3-11 are not shown. Figures 1-10 The moisture content of each product is determined by a moisture meter, and the mass of the recovered product in Examples 1-8 and Comparative Examples 1-11 is obtained. The results are shown in Table 1 below.

[0109] Table 1: Effect of pH value and type of solvent on the mass and GC purity of the recovered product of each example:

[0110]

[0111] As shown in Table 1, the product with high purity of 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane can be obtained by the method of the present application; the wastewater is treated, the pH of the wastewater is adjusted to the range of 12 to 14, and the organic solvent such as dichloromethane, toluene or ethyl acetate can be used to recover the product with the mass of not less than 80 g per liter of wastewater, and the purity of 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane is higher than 98%, especially, when the pH of the wastewater is adjusted to 14, the volume ratio of the wastewater to the organic solvent is 10: (1-2), the organic solvent is dichloromethane or toluene, and the fraction of 190-200℃ is collected, the mass of the product recovered per liter of wastewater is not less than 90 g, and the purity is not less than 98.8%; but when the pH of the wastewater is adjusted to 14 and the distillation condition of the present application is not used, the product obtained is impure, which affects the mass and purity of the recovered product.

[0112] In the description of the present specification, the description of the terms "one embodiment", "another embodiment", "yet another embodiment", "some embodiments", "other embodiments" and the like means that the specific features, structures, materials or characteristics described in connection with the embodiment are included in at least one embodiment of the present application. In the present specification, the illustrative description of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any appropriate manner in any one or more embodiments or examples. In addition, the person skilled in the art can combine and combine the different embodiments or examples described in the present specification and the features of the different embodiments or examples without contradiction. In addition, it should be noted that in the present specification, the terms "first", "second" are used for the purpose of description only, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features.

[0113] Although the embodiments of the present application have been shown and described above, it should be understood that the above embodiments are exemplary and cannot be understood as limiting the present application, and the person skilled in the art can make changes, modifications, replacements and variations to the above embodiments within the scope of the present application.

Claims

1. A process for the recovery of 5-(N-ethyl-N-hydroxyethyl)-2- aminopentane, characterized in that, The method comprises the following steps: 1) adjusting the pH value of wastewater to 12-14 to obtain a first mixed solution; 2) adding an organic solvent to the first mixed solution to extract to obtain an organic phase containing 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane; 3) concentrating the organic phase under reduced pressure to obtain a concentrated solution; 4) distilling the concentrated solution under reduced pressure, and collecting a fraction at 190-200 DEG C to obtain 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane by heating to 195-210 DEG C, wherein the wastewater is generated from the treatment of amine reaction wastewater in the synthesis of hydroxychloroquine; the organic solvent is selected from at least one of dichloromethane, toluene and ethyl acetate.

2. The method of claim 1, wherein, In step 3), the temperature for concentrating the organic phase under reduced pressure is 30-110 DEG C.

3. The method of claim 1, wherein, In step 2), the volume ratio of the wastewater to the organic solvent is 10:(1-2).

4. The method of claim 1, wherein, The organic solvent is dichloromethane.

5. The method of claim 4, wherein, In step 3), the temperature for concentrating the organic phase under reduced pressure is 30-60 DEG C.

6. The method of claim 1, wherein, The organic solvent is toluene.

7. The method of claim 6, wherein, In step 3), the temperature for concentrating the organic phase under reduced pressure is 70-110 DEG C.

8. The method of claim 1, wherein, The organic solvent is ethyl acetate.

9. The method of claim 8, wherein, In step 3), the temperature for concentrating the organic phase under reduced pressure is 50-80 DEG C.

10. The method of claim 1, wherein, In step 3), further comprising recovering the organic solvent after concentrating the organic phase under reduced pressure.

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