Method for producing a mixture containing 2-(2-hydroxyethyl)-piperidinylcarbamic acid secondary butyl ester

Abstract

The present invention relates to an improved method for producing a mixture comprising 2-(2-hydroxyethyl)-piperidinylcarbamic acid secondary butyl ester from a product by means of heat treatment with a very short residence time, an apparatus for the said method, the use of such an apparatus for such a method, and the mixture according to the present invention that can be obtained by using the said method. [Solution] A mixture comprising, as components, 98.8% to 100.0% by weight, preferably 99.0% to 99.9% by weight, of a compound of formula (I), 0.00% to 0.60% by weight, preferably 0.0001% to 0.20% by weight, of a compound of formula (II), and further components, wherein the total weight percentages of the components amount to 100% by weight, and the mixture has a Hazen color number of 0 to 15 as measured by the DIN EN ISO 6271 method.

Description

Technical Field

[0001] The present invention relates to an improved process for producing a mixture containing sec-butyl 2-(2-hydroxyethyl)piperidinylcarbamate from a crude reaction product by heat treatment using a short residence time, an apparatus for such a process, the use of such an apparatus for such a process, and a mixture of the present invention obtainable from such a process.

Background Art

[0002] Sec-butyl 2-(2-hydroxyethyl)piperidinylcarbamate [also called 1-piperidinecarboxylic acid 2-(2-hydroxyethyl)-1-methylpropyl ester; CAS No. 119515-38-7, International Nonproprietary Name (INN): Icaridin, Picaridin, Saltidin (registered trademark), commercial product: Saltidin (registered trademark) (manufactured by Saltigo GmbH (Leverkusen, Germany))] has the following Formula (I):

Chemical

[0003] This molecule contains two stereocenters. In the present invention, formula (I) includes the individual four possible stereoisomers, as well as various mixtures and racemates, i.e., mixtures of individual stereoisomers or mixtures of equimolar pairs of the two possible enantiomers.

[0004] This compound is a highly effective and tolerated insect repellent against mosquitoes and mites and is commercially available in various formulations for application to the skin of humans and animals.

[0005] A method for preparing sec-butyl 2-(2-hydroxyethyl)piperidinylcarbamate is described, for example, in (Patent Document 1), according to which sec-butyl 2-(2-hydroxyethyl)piperidinylcarbamate is obtained in a theoretical yield of 89 percent (based on 2-(2-hydroxyethyl)piperidine). In the final stage, 2-(2-hydroxyethyl)piperidine is chemically reacted with sec-butyl chloroformate in the presence of an immiscible solvent and a base. This reaction produces, in addition to the desired reaction product, secondary components such as sodium chloride and organic compounds, some of which may be discolored and / or have an unpleasant odor. For example, (Patent Document 1) states that the crude reaction product from this reaction is often contaminated and therefore must be purified by distillation or chromatography, which can result in a considerable decrease in yield in addition to increased cost and effort. Furthermore, it has been noted that the main side reaction results in the formation of a reaction product induced by a competitive reaction between the chloroformate ester and the hydroxyl group from 2-(2-hydroxyethyl)piperidine.

[0006] For example, according to a commonly used and known manufacturing process, equation (II): [ka] The compound is present in a content of approximately 1% by weight or more. In addition, mixtures prepared by conventional processes containing the compound of formula (I) in an amount greater than 90% by weight have a Hazen color number greater than 40.

[0007] In purification by distillation at low pressure, decomposition reactions can occur, and the resulting malodorous reaction products may contaminate the distillate. Therefore, at present, it has been impossible to use distillation at a satisfactory level as a purification method for sec-butyl 2-(2-hydroxyethyl)piperidinylcarbamate on an industrial scale.

[0008] Therefore, typically, the reaction mixture remaining after the reaction is subject to an aqueous work-up, in which case it is necessary to neutralize the various bases present by adding an acid. Typically, this is followed by the removal of the organic phase, which contains the desired reaction product and organic secondary components, as well as the water-immiscible organic solvent used in the reaction, such as hexane or toluene. On an industrial scale, such as when the reaction product is produced in batch sizes exceeding 1000 kg, it has been found that several washes of the thus obtained organic phase, containing water and / or acid, are necessary to obtain a reaction product that meets the purity, color, and olfactory quality requirements suitable for producing insect repellent formulations. After the washes, the solvent is typically distilled off the organic phase under reduced pressure, leaving all or part of the reaction product and organic and inorganic secondary components / impurities in the bottom liquid. The bottom liquid is then withdrawn from the reactor, filtered, and constitutes the final product. In processes currently implemented on an industrial scale, the reaction product of sec-butyl 2-(2-hydroxyethyl)piperidinylcarbamate is obtained by this method in a yield of approximately 90 percent of the theoretical value based on 2-(2-hydroxyethyl)piperidine and a purity of 97.0–98.5% by weight. It typically has a Hazen color number of 40 or more and a slight, characteristic unpleasant odor. Although this current best process makes it possible to obtain sec-butyl 2-(2-hydroxyethyl)piperidinylcarbamate in very good yield and purity, even on an industrial scale, conventional processes still have the drawbacks of being extremely complex to work up the crude reaction product, consuming a lot of energy, and generating a large amount of waste, thus resulting in high costs.

[0009] However, prior art also discloses a method for synthesizing sec-butyl 2-(2-hydroxyethyl)piperidinylcarbamate, which involves reacting 2-(2-hydroxyethyl)piperidine with sec-butyl chloroformate in the presence of a solvent, followed by several extraction washes of the organic phase, and finally, distilling the reaction product under reduced pressure.

[0010] For example, (Patent Document 2) describes the reaction of 2-(2-hydroxyethyl)piperidine with sec-butyl chloroformate in the presence of a solvent such as dichloromethane, chloroform, benzene, toluene, tetrahydrofuran, n-hexane, cyclohexane, or methylcyclohexane. The base used is an organic base such as 2-(2-hydroxyethyl)piperidine, triethylamine, pyridine, or trimethylamine. The organic phase containing the crude reaction product was repeatedly washed with water and sodium chloride solution. The organic phase was then dried with sodium sulfate or magnesium sulfate, filtered, and the solvent was removed by distillation. The residue was then distilled to obtain the reaction product as a distillate with a boiling point of 140-152°C at 5 mmHg (6.67 hPa). For batch sizes of approximately 20 kg of reaction product, this process yielded a reaction product with an area percentage content of 97.5-98.0 (confirmed by gas chromatography) in a theoretical yield of 84-87 percent.

[0011] However, in in-house experiments (see Examples), when the crude reaction product obtained after several aqueous washes was distilled under reduced pressure of 20 hPa and a column bottom temperature of approximately 175°C, significant decomposition of the reaction product occurred, and 2-butanol was dissociated, resulting in formula (III): [ka] It was found that a cyclic carbamate of 2-(2-hydroxyethyl)piperidine is formed, and typically, condensation of butanol does not occur in the condenser where the reaction product of formula (I) condenses, but only in the downstream cold trap, leaving the carbamate in the bottom liquid.

[0012] Since batch distillation at less than 10 hPa is virtually impossible on an industrial scale, the work-up procedure described in (Patent Document 2) is not a viable option for this purpose.

[0013] Furthermore, at present, reaction products containing the compound of formula (I) in amounts exceeding 90% by weight, which are obtainable on an industrial scale, have a slight but unpleasant odor that may be undesirable in insect repellent formulations and would require masking with fragrances. [Prior art documents] [Patent Documents]

[0014] [Patent Document 1] European Patent Application Publication No. 0 537 534A1 Specification [Patent Document 2] Chinese Patent Application Publication No. 102167681A1 Specification [Overview of the Initiative] [Problems that the invention aims to solve]

[0015] The industrial problem remaining thus is to provide a process for preparing sec-butyl 2-(2-hydroxyethyl)piperidinylcarbamate which does not have the drawbacks of the prior art processes. Thus, there has been a need for an improved process which, on an industrial scale, gives 2-(2-hydroxyethyl)piperidinylcarbamate with at least comparable yields and purity, or even higher yields, and / or with a low level of unwanted secondary components, and / or with better hue quality and / or olfactory quality, consuming less time and energy and producing less waste. For this, the technical problem has been to provide such an improved process.

Means for Solving the Problems

[0016] Now, surprisingly, there has been found an improved process for producing a mixture comprising, as components, 98.8% to 100.0% by weight, preferably 99.0% to 99.9% by weight, of a compound of formula (I):

Chemical formula

Chemical formula

[0017] Furthermore, compounds of formula (I) were found as components in an amount of 98.8% to 100.0% by weight, preferably 99.0% to 99.9% by weight: [ka] Compounds of formula (II) in amounts of 0.00% to 0.70% by weight, preferably 0.00% to 0.6% by weight, more preferably 0.00% to 0.5% by weight, and especially preferably 0.0001% to 0.20% by weight; [ka] A further embodiment of the process of the present invention for producing a mixture comprising further components (where the weight percentages of those components total 100% by weight, and the mixture has a Hazen color number of 0 to 15 as measured by DIN EN ISO 6271), starting from a crude reaction product comprising the following: ○A compound of formula (I) in an amount of 94% to 98.0% by weight, and Here, at least fraction A (distillate, mixture of the present invention) is separated from fraction B (bottom liquid) and gas fraction C by the following steps: a) A step of heat-treating the crude reaction product in liquid phase to form a gas stream G containing fractions A and C, and leaving fraction B as the liquid phase, and b) Simultaneously and / or subsequently, the step of withdrawing fraction B from the process in liquid form, c) Simultaneously and / or subsequently, the step of condensing fraction A from gas stream G and withdrawing it from the process to obtain the mixture of the present invention, d) In some cases, simultaneously and / or subsequently, a step of condensing fraction C and removing it from the process, Herein, in a further embodiment of the process of the present invention, the residence time of the liquid phase during the heat treatment, preferably the residence time of the liquid phase containing the crude reaction product and / or fraction B or various mixtures thereof, is 1 to 900 seconds, preferably 10 to 600 seconds, more preferably 10 to 300 seconds.

[0018] The process of the present invention also suitably produces a mixture comprising, as components, 98.8% to 100.0% by weight, preferably 99.0% to 99.9% by weight of the compound of formula (I), 0.00% to 0.70% by weight, preferably 0.0001% to 0.20% by weight of the compound of formula (II), 0.0001% to 2.0% by weight of the compound of formula (III), and further components, wherein the sum of the weight ratios of these components is 100% by weight, and the mixture has a Hazen color number of 0 to 15 as measured by the DIN EN ISO 6271 method.

[0019] In a further embodiment, the process of the present invention can also suitably produce a mixture comprising, as components, 98.8% to 100.0% by weight, preferably 99.0% to 99.9% by weight of the compound of formula (I), 0.00% to 0.60% by weight, preferably 0.0001% to 0.20% by weight of the compound of formula (II), 0.0001% to 2.0% by weight of the compound of formula (III), and further components, wherein the sum of the weight ratios of these components is 100% by weight, and the mixture has a Hazen color number of 0 to 15 as measured by DIN EN ISO 6271.

[0020] In a further embodiment, the process of the present invention can also suitably produce a mixture comprising, as components, 98.8% to 100.0% by weight, preferably 99.0% to 99.9% by weight of the compound of formula (I), 0.00% to 0.50% by weight, preferably 0.0001% to 0.20% by weight of the compound of formula (II), 0.0001% to 2.0% by weight of the compound of formula (III), and further components, wherein the sum of the weight ratios of these components is 100% by weight, and the mixture has a Hazen color number of 0 to 15 as measured by DIN EN ISO 6271.

[0021] In the process of the present invention, a crude reaction product obtained by a chemical manufacturing process, and then typically by a purification step of an extraction method, is used.

[0022] In the process of the present invention, it is equally preferable to use a crude reaction product comprising 94.0% to 99.0% by weight of the compound of formula (I) and 0.50% to 5.0% by weight of the compound of formula (II), and having a Hazen color number of at least 40 as measured by DIN EN ISO 6271.

[0023] In the process of the present invention, it is equally preferable to use a crude reaction product comprising 94.0% to 98.0% by weight of the compound of formula (I) and having a Hazen color number of at least 40 as measured by the DIN EN ISO 6271 method.

[0024] For example, the crude reaction product is produced by a method comprising the following steps: i. A step of reacting 2-hydroxyethylpiperidine with sec-butyl chloroformate in the presence or absence of at least one base and at least one solvent to obtain a reaction mixture containing 35% to 65% by weight of the compound of formula (I), and ii. The next step, if applicable, is to add acid and / or water to the reaction mixture from step i. while mixing to form a two-phase reaction mixture containing an organic phase and an aqueous phase, and iii. Then, optionally, a step of separating the organic phase from the aqueous phase of the reaction mixture from step ii, and iv. Next, if applicable, the organic phase from step iii. is washed with an acidic aqueous solution, and v. Next, if applicable, a step of drying the organic phase from step iv, and vi. The next step, if applicable, is to separate at least one solvent from the organic phase from step v. to obtain the crude reaction product.

[0025] In one preferred embodiment, this crude reaction product can be used in the process of the present invention.

[0026] In the process of the present invention, three different fractions are separated, where fraction A is the mixture of the present invention, fraction B, which has a higher boiling point, is a mixture typically containing 40% to 95% by weight of the compound of formula (I) and 1.5% to 50% by weight of the compound of formula (II), and fraction C, which has a lower boiling point, is a mixture typically containing 0.0% to 0.5% by weight of the compound of formula (I), and depending on the quality of the starting materials, substantially containing water, butanol, and toluene. In the process of the present invention, the liquid crude reaction product as a liquid phase is subjected to heat treatment by appropriate technical means. It is essentially important for the process of the present invention that the residence time of the liquid phase during heat treatment, preferably the residence time of the liquid phase containing the crude reaction product and / or fraction B or various mixtures thereof, is 1 to 900 seconds, preferably 10 to 600 seconds, more preferably 10 to 300 seconds.

[0027] As should be obvious, residence time represents the time from the start of the heat treatment of the crude reaction products, that is, the time when the crude reaction products are first introduced into the region in which the heat treatment is performed, through the depletion of the crude reaction products in the gas stream G within the region in which the heat treatment is performed, accompanied by the formation of fraction B (which therefore exists), to the end of the heat treatment, that is, the time when fraction B leaves the region in which the heat treatment is repeatedly performed.

[0028] The heat treatment of the crude reaction product is preferably carried out by bringing the crude reaction product into contact with a fixed heating surface.

[0029] In the present invention, the residence time of the liquid phase during heat treatment is measured using the heat input at the temperature and pressure in which the process of the present invention is carried out. Those skilled in the art will know of methods for this purpose. For example, the residence time can be confirmed by a method called the tracer method. Typically obtained from these measurements is a residence time distribution (RTD) curve. The average residence time can then be calculated by a conventional method. The average residence time can also be obtained with sufficient accuracy by a simplified method. For example, in a continuous process in equilibrium, the average residence time T (measured in seconds) is the quotient of, for example, the volume V (measured in cubic centimeters) of the liquid phase in the space in which the heat treatment is carried out, and / or the flow rate R (measured in cubic centimeters / second) of the liquid phase into the space in which the heat treatment is carried out, i.e., V / R. In the present invention, the residence time is the average residence time calculated from the measured residence time distribution and / or obtained by a simplified method.

[0030] The process of the present invention does not employ a distillation process in which the liquid phase is heat-treated during operation, and the entire original liquid phase is heated in a certain volume to evaporate and remove its volatile components. In these so-called batch distillations, the residence time depends on the distillation time. When the distillates are simultaneously withdrawn, for example, the average residence time, measured in cubic centimeters per second, corresponds to half the distillation time of the liquid phase in batch distillation.

[0031] In the preferred process of the present invention, the stationary surface is heated to a temperature sufficient to generate a gas stream G containing fractions A and C. Fraction B does not convert to a gas phase on the heated stationary surface, but rather is transferred from the heated surface as a liquid film to a tank prepared for fraction B by technical means. The gas stream G has a boiling point of approximately 330°C at atmospheric pressure, 178–182°C at 20 hPa, and 194–190°C at 35 hPa, and at 20 hPa, it typically has a temperature of 170–180°C, measured at the top of the evaporating space.

[0032] In the process of the present invention, the gas stream G is preferably generated at a temperature of 120 to 200°C, preferably 120 to 185°C, more preferably 120 to 175°C, and at a pressure of 1 to 35 hPa, preferably 1 to 21 hPa, more preferably 2 to 15 hPa. Higher pressures, and consequently higher temperatures required to generate the gas stream G, increase the decomposition of the compound of formula (I). At the aforementioned pressures, it is preferable to select a temperature of 40°C or less, preferably 30°C or less, higher than the boiling point of fraction A, i.e., the mixture of the present invention, at the corresponding pressure.

[0033] In the process of the present invention, fraction A is typically removed from the gas stream G by condensation, preferably via a condenser, through appropriate technical means. In this case, condensation is preferably carried out at a pressure of 2 to 5 hPa and a temperature of 80 to 100°C, or under appropriate boiling temperature-pressure conditions. During this condensation, fraction C remains in the gas phase.

[0034] In one embodiment of the process of the present invention, fraction C can also be condensed at a pressure of 2 to 5 hPa at a temperature of -10 to 30°C, or under appropriate boiling temperature-pressure conditions. In a further embodiment of the process of the present invention, fraction C may be left in a gaseous state and disposed of, for example, by incineration.

[0035] It is preferable to carry out the process in a continuous manner. In this case, the crude reaction product is subjected to continuous heat treatment, while fraction B is discharged from the process in liquid form, and at the same time, a gas stream G is generated and removed from the heat treatment technical means, preferably from its fixed heating surface. In this case, fraction A, and possibly fraction C, are condensed at the same time. This means that in the process of the present invention, these various operating operations are in equilibrium. In this equilibrium, it is essential that the mass of the crude reaction product added to the process is always equal to the sum of the masses of fractions A, B, and C discharged from the process. In this context, "essentially important" means that variations in the mass flow rate per unit time due to technical reasons are included.

[0036] A further advantage of a preferred embodiment of the process of the present invention is that no co-retention agent is added to the crude reaction product at any point in the process. This avoids the generation of further waste. A co-retention agent typically refers to a liquid substance added to the mixture to be distilled, e.g., the crude reaction product. These co-retention agents generally have a higher boiling point than the components in the form of a gas stream, e.g., fraction A and / or fraction C, separated from the bottom liquid, e.g., fraction B, and form a homogeneous phase with the mixture to be distilled. They are chemically inert and therefore do not react with the components of the mixture to be distilled. Co-retention agents generally increase the yield of the distillate.

[0037] The present invention also encompasses an apparatus of the present invention that includes at least an evaporation unit (1), a tank (3) for fraction B, a condenser (5), and a pump (8).

[0038] Preferably, the apparatus of the present invention further includes a column (4), a connecting conduit (11) between the evaporation unit (1) and the column (4), a reflux divider (6), and a condenser (7).

[0039] The apparatus of the present invention more preferably further includes: an inlet (21) for crude reaction products, a connecting conduit (41) between column (4) and condenser (5), a connecting conduit (51) between condenser (5) and condenser (7), an outlet (72) for fraction C, a connecting conduit (61) between condenser (5) and reflux divider (6), a connecting conduit (62) between column (4) and reflux divider (6), and an outlet (63) for fraction A. [Brief explanation of the drawing]

[0040] [Figure 1] Figure 1 shows a flowchart of a particularly preferred apparatus of the present invention. [Modes for carrying out the invention]

[0041] The markings in Figure 1 mean the following: 1 Evaporation Unit 2. Vessel for crude reaction product 3. Tank for fraction B 4 columns 5. Condenser 6. Refrigerant Diverter 7. Condenser 8 pumps 11 Outlet for gas stream G, conduit between 1 and 4 21 Inlet for crude reaction product 31 Exit for Fraction B 41 Connecting conduit between 4 and 5 51 Connecting conduit between 5 and 7 61 Connecting conduit between 5 and 6 62 Connecting conduit between 6 and 4 63 Exit for Fraction A 71 Connecting conduit between 6 and 7 72 Exit for fraction C

[0042] In one embodiment, the process of the present invention is carried out in an apparatus that includes at least the following: • Evaporation unit (1), inlet (21) for crude reaction product, and outlet (31) for fraction B: ○Here, the evaporation unit (1) includes at least the following: ○A heatable housing shell enclosing a rotationally symmetric evaporation space extending in the axial direction, and A drivable rotor shaft, extending coaxially within the evaporation space, is provided for forming a film of crude reaction products on the inner surface of the housing shell and for moving the substance from the inlet (21) for the crude reaction products toward the outlet (31) for fraction B, wherein the rotor shaft has a central rotor shaft body and rotor elements arranged around it, the radially outermost end of which is located slightly away from the inner surface of the housing shell. • Condenser (5), reflux divider (6), outlet (63) for fraction A, and preferably column (4): Here, in step a), the crude reaction product is introduced into the evaporation space of the evaporation unit (1) via the inlet (21), subjected to heat treatment, and a liquid film of the crude reaction product is formed on the inside of the housing shell, and as a result the liquid film of the crude reaction product is heated to a temperature in which at least a portion of fractions A and C are converted into a gaseous state and discharged from the evaporation unit (1), preferably via the outlet (11), as a gas stream G, where the ratio of mass flow rates between fraction B and gas stream G is from (1:20) to (1:5), and ○In step b), fraction B is discharged from the evaporation unit (1) through the outlet (31), and then, ○In step c), the gas stream G moves from the evaporation unit (1), preferably through the column (4), into the condenser (5), where fraction A is condensed and obtained through the reflux divider (6) and outlet (63).

[0043] Preferably, the apparatus of the present invention further includes a condenser (7) in which fraction C is optionally condensed in step d), and fraction C is optionally discharged through an outlet (72) for fraction C.

[0044] It is preferable that the evaporation unit 1 is a thin-film evaporator or a falling-film evaporator. It is more preferable that the evaporation unit 1 is a thin-film evaporator.

[0045] The evaporation unit 1 is typically cylindrical and has an outer housing shell and an inner housing shell. The housing shell may have a single shielding wall design or a double shielding wall design. A double shielding wall design is advantageous because there is a temperature difference between the inner and outer parts of the evaporation unit 1. This makes it possible to incorporate insulating and / or heating elements in the gap, thereby enabling extremely precise temperature control on the inner surface of the housing shell, i.e., the inner housing shell. In this context, "inside" always means the side of the surface facing the center of the cross-section of the cylindrical evaporation space. A motor-driven rotor exists, coaxially arranged with respect to the rotationally symmetric evaporation space whose outer circumference is defined by the inner surface of the housing shell, and consisting of a rotor shaft and rotor elements mounted thereon. The rotor elements extend radially from the center of the rotor shaft toward the inner surface of the housing shell. A rigid and dynamic rotor element exists.

[0046] Rigid rotor elements include, for example, rigid blade rotors, radial wiper rotors, or wiper blade rotors. In this case, the ends of the inflexible segments located very close to the inner surface of the housing shell, or the flexible segments, such as the movable blade or wiper, are pressed toward the inner surface of the housing shell due to the elasticity of the material and / or the centrifugal force resulting from the rotation of the rotor. If no reaction products are present, the ends of these flexible elements will be able to contact the inner surface of the housing shell. In the case of dynamic rotors, for example, moving rollers are used, which are attached to movable arms and further connected to the rotor axis. The centrifugal force resulting from the rotation of the rotor presses these rollers toward the inner surface of the housing shell, and as a result, if no reaction products are present in the evaporation space, they will be able to contact the inner surface of the housing shell. However, if a reaction product containing evaporable components is introduced into the evaporation space, this reaction product is directed by appropriate technical means toward the upper portion of the inner surface of the housing shell and then dispersed as a film on the inner surface of the housing shell by the end segments of the rotor, by means of the gap existing between them and the outermost end of a rigid blade, or by means of the flexible end segments of a wiper or roller. In this case, the thickness of the film is controlled at least by the interaction between the viscosity of the reaction product and the type and speed of the rotor and rotor elements.

[0047] In one preferred embodiment of the process of the present invention, the crude reaction product is heat-treated in the form of a liquid film having a thickness of 0.001 to 2 mm, preferably 0.005 to 1 mm.

[0048] In one preferred embodiment of the process of the present invention, the crude reaction product is subjected to heat treatment as a liquid film having a thickness of 0.001 to 2 mm, preferably 0.005 to 1 mm, by bringing it into contact with a fixed heating surface.

[0049] A further preferred embodiment of the process of the present invention is that the crude reaction product is heat-treated in the evaporation unit 1 in the form of a liquid film having a thickness of 0.001 to 2 mm, preferably 0.005 to 1 mm. In this further preferred embodiment, the inner surface of the housing shell of the evaporation unit (1) forms a heated fixed surface that comes into contact with the crude reaction product.

[0050] The film thickness is determined by the technical parameters of the apparatus used for the purpose and the technical means used. This will be explained in more detail below. The liquid film is in direct contact with a fixed heating surface. The fixed heating surface may be, for example, the inner wall of a thin film evaporator or a flowing film evaporator. It is preferable that the fixed surface is the inner wall of a thin film evaporator.

[0051] The film thickness is determined, for example, by bringing a predetermined reaction product into contact with a fixed heating surface at a temperature adopted in the preferred process of the present invention, at a predetermined flow rate and standard pressure. What is measured here is the time required to completely wet the fixed heating surface as the film forms. The measurement time T is, for example, 120 seconds, and the flow rate R is, for example, 300 cm³. 3 T×R, which is the product of / 3600 seconds, is the volume V of the film formed on the entire surface area of ​​the fixed heating surface, for example, 10 cm³. 3 The area of ​​the fixed heating surface A can be calculated, for example, from its shape data, so the film thickness F can be calculated by dividing the quotient V / A, i.e., the volume of the film by the area of ​​the fixed heating surface A. In the previous example, the surface area A was 1000 cm². 2 Therefore, the film thickness is 0.01 cm. Assuming no evaporation of the reaction product fraction, the average residence time of the reaction product on the fixed heated surface in this example is 120 seconds. On the other hand, if the area A is known and the volume required to wet the entire area A with flow rate R is measured, it is also possible to determine the average residence time.

[0052] In the preferred process of the present invention, the residence time of the liquid components, i.e., the crude reaction product and / or fraction B, or various mixtures thereof, on the fixed heated surface is preferably 1 to 900 seconds, more preferably 10 to 600 seconds, and particularly preferably 10 to 300 seconds.

[0053] In the preferred process of the present invention, when using an evaporation unit (1), for example a thin-film evaporator, a film thickness of 0.001 to 2 mm, preferably 0.001 to 1 mm, is employed. In this case, the film thickness is determined, for example, by measuring the time required to completely wet the inner surface of the housing shell to form a film at a predetermined flow rate of a specific reaction product processed in the evaporation unit 1, for example in the thin-film evaporator, at a predetermined rotor speed of the evaporation unit 1 and a predetermined temperature (but at standard pressure) of the inner surface of the housing shell. The measurement time T is for example 50 seconds and the flow rate R is for example 300 cm³. 3 The product of T × R with / 3600 seconds is the volume of the film to be produced, for example, 5 cm³. 3 This provides a film that is formed by the rotor on the entire inner surface of the housing shell. Since the inner surface area A of the housing shell can be calculated, for example, from its shape data, it is possible to calculate the film thickness F as the quotient V / A, i.e., the volume of the film divided by the inner surface area A of the housing shell. In the previous example, the film thickness is 0.05 mm. In this example, the average residence time of the liquid phase in evaporation unit 1 is 60 seconds.

[0054] In the preferred process of the present invention, the residence time of the liquid components, i.e., the crude reaction product and / or fraction B, or various mixtures thereof, on the fixed heated surface is 1 to 900 seconds, preferably 10 to 600 seconds, and particularly preferably 10 to 300 seconds.

[0055] In the preferred process of the present invention using the evaporation unit 1, it is preferable to select the temperature for the inner surface of the housing shell to be 40°C or less higher than the boiling point of fraction A, preferably 30°C or less higher, at each pressure. In step a), it is equally preferable to convert the gas stream G into a gas phase by bringing it into contact with the inner surface of the housing shell of the evaporation unit (1) at a temperature of 120 to 200°C, preferably 120 to 185°C, more preferably 120 to 175°C, and a pressure of 1 to 35 hPa, preferably 1 to 21 hPa, more preferably 2 to 15 hPa.

[0056] In this case, the crude reaction product is introduced, preferably through the inlet 21 and by appropriate technical means, into the upper portion of the evaporation unit 1, directly onto the upper portion of the heated inner surface of the housing shell of the evaporation unit 1. This initiates downward flow due to gravity, and the segmented ends of the rotor element begin to homogeneously disperse the crude reaction product as a liquid film on the heated inner surface of the housing shell of the evaporation unit 1. Those skilled in the art will be able to determine the optimal wiping speed of the rotor for the evaporation unit 1 with simple experiments. If the wiping speed is too slow, the distribution of the liquid film will be incomplete, and droplets will likely form, but these droplets will pass through the evaporation unit 1 at a faster rate than the liquid film. If the wiping speed exceeds the optimal value, further increasing the wiping speed will not result in any further improvement of the liquid film. As crude reaction products are replenished, due to gravity and the mechanical force at the rotating end of the rotor element, the liquid film of crude reaction products gradually moves toward the lower end of the heated inner surface of the housing shell of the evaporation unit 1. Upon contact between the liquid film of crude reaction products and the heated inner surface of the housing shell of the evaporation unit 1, a portion of the crude reaction products is converted into a gas phase as a gas stream G containing fractions A and C. Fraction B, which is not converted into a gas phase at the heated inner surface of the housing shell of the evaporation unit 1, moves in liquid form, continuously toward the bottom of the evaporation unit 1 where the outlet 31 for fraction B is located, due to gravity and / or the motion of the rotor element. Due to the pressure gradient generated by condensation, the gas stream G moves toward the upper part of the evaporation unit 1 where the outlet 11 for gas stream G is located. Preferably, the outlet 11 is connected to a column 4. More preferably, the column 4 is a column containing internal components, random packing, or fixed packing. Column 4 preferably has 1 to 20 theoretical stages, more preferably 5 to 15 stages, and more preferably 8 to 12 stages.

[0057] Inside column 4, in the preferred process of the present invention, there exists a vapor-condensate equilibrium state with an upward concentration gradient. In this concentration gradient, the proportion of higher boiling point components increases towards the bottom of the column. In this preferred embodiment, a portion of the gas stream G is continuously withdrawn in gaseous form from the top of column 4 and enters the condenser 5 via a conduit 41 connected to the condenser 5. The condenser 5 typically has an internal temperature of 50 to 110°C, preferably 70 to 110°C, and condenses fraction A, while fraction C is withdrawn in gaseous form from the upper part of the condenser 5 via an outlet 51. The condensed fraction A is preferably withdrawn from the condenser 5 via an outlet 61 connected to a conduit connected to a reflux divider 6. A portion of the condensed fraction A is withdrawn from the reflux divider 6 via the outlet 63, while another portion of the condensed fraction A flows back from the reflux divider 6 under gravity through the conduit 62 connected to the upper part of the column 4.

[0058] In a particularly preferred embodiment of the process of the present invention, the reflux in the reflux splitter 6 is adjusted so that the ratio of mass flow rates exiting the reflux splitter 6 from conduit 62 and conduit 63 is from (1:10) to (1:1), preferably from (1:5) to (1:2). For example, when the mass flow rate is (1:10), the reflux splitter 6 discharges 10 times more mass of condensed fraction A through conduit 63 than the mass of fraction A exiting the reflux splitter 6 through conduit 62 and returning to column 4. Through the conduit 63, a mixture of the present invention is obtained, comprising 98.8% to 100.0% by weight, preferably 99.0% to 99.9% by weight, of the compound of formula (I) in the form of fraction A, and 0.00% to 0.70% by weight, preferably 0.0001% to 0.20% by weight, of the compound of formula (II), and having a Hazen color number of 0 to 15 as measured by DIN EN ISO 6271.

[0059] The condensed fraction A, which flows back into the column through the conduit 62, partially flows further back into the evaporation unit 1.

[0060] In one preferred embodiment of the process of the present invention, the gas stream G is generated at a pressure of 1 to 30 hPa. The gas stream G is typically at a pressure of 20 hPa and a temperature of 170 to 180°C. Higher pressures, and consequently higher temperatures required to generate the gas stream G, increase the decomposition of the compound of formula (I). At the aforementioned pressures, it is preferable to select the temperature of the inner wall surface of the evaporation unit 1 to be above the boiling point of fraction A, but 40°C or less, preferably 30°C or less, for each respective pressure. It is equally preferable that its heated fixed surface be heated to a temperature of 120 to 200°C, preferably 120 to 185°C, more preferably 120 to 175°C, and a pressure of 1 to 35 hPa, preferably 1 to 21 hPa, more preferably 2 to 15 hPa.

[0061] It is preferable to carry out the process of the present invention continuously. This includes continuously generating a liquid film of the crude reaction product in the evaporation unit 1, simultaneously withdrawing fraction B in liquid form from the process via outlet 31, and simultaneously transferring the gas stream G into column 4 via outlet 11, and then transferring it into condenser 5 via conduit 41.

[0062] Simultaneously, fraction A is then condensed in condenser 5, and fraction C is optionally condensed in condenser 7, and optionally discharged from the process through an outlet (72) for fraction C. In condenser 7, an internal temperature of -10 to +30°C, preferably 0 to +30°C, is typically maintained. This means that during the process of the present invention, these various operating operations are in equilibrium. In this equilibrium, it is essential that the mass of the crude reaction product added to the process is always equal to the sum of the masses of fractions A, B, and C discharged from the process. In this context, "essentially important" means that variations in the individual mass flow rate per unit time due to technical reasons are included.

[0063] In a particularly preferred embodiment of the process of the present invention, the mass flow rate of fraction B is adjusted so that the mass ratio of fraction A discharged from the process through pipe 63 to fraction B discharged from the process through outlet 31 is continuously from (4:1) to (49:1), preferably from (5:1) to (10:1). It is preferable that fraction B discharged from the process through outlet 31 contains 40% to 95% by weight of the compound of formula (I) and 1.5% to 50% by weight of the compound of formula (II).

[0064] In a more particularly preferred embodiment of the process of the present invention, fraction B is collected and then reintroduced into the evaporation unit 1 as a crude reaction product, in which case fractions AA and BB are formed. This increases the chemical yield of the mixture of the present invention without the composition of the resulting mixture of the present invention deviating from the limits of the claims.

[0065] The present invention also relates to a process for producing the mixture of the present invention in the apparatus of the present invention.

[0066] The present invention also relates to a mixture obtainable by the process of the present invention, comprising 98.8% to 100.0% by weight, preferably 99.0% to 99.9% by weight, of the compound of formula (I), and 0.00% to 0.70% by weight, preferably 0.0001% to 0.20% by weight, of the compound of formula (II), and having a Hazen color number of 0 to 15 as measured by DIN EN ISO 6271.

[0067] The present invention also relates to a mixture that can be obtained by the process of the present invention, comprising 98.8% to 100.0% by weight, preferably 99.0% to 99.9% by weight, of the compound of formula (I), and 0.00% to 0.60% by weight, preferably 0.0001% to 0.20% by weight, of the compound of formula (II), and having a Hazen color number of 0 to 15 as measured by DIN EN ISO 6271.

[0068] The present invention also relates to a mixture that can be obtained by the process of the present invention, comprising 98.8% to 100.0% by weight, preferably 99.0% to 99.9% by weight, of the compound of formula (I), and 0.00% to 0.50% by weight, preferably 0.0001% to 0.20% by weight, of the compound of formula (II), and having a Hazen color number of 0 to 15 as measured by DIN EN ISO 6271.

[0069] Preferably, the mixture of the present invention further contains 0.0001% to 2.0% by weight of the compound of formula (III). A further advantage of the mixture of the present invention is that it is possible to produce a significantly lower odor than currently known reaction products containing more than 90% by weight of the compound of formula (I). This can be clearly demonstrated in double-blind olfactory tests.

[0070] The process of the present invention remarkably overcomes the shortcomings of prior art processes and makes it possible to obtain a mixture containing the compound of formula (I) in a favorable composition previously unknown. At the same time, the process of the present invention has a chemical yield of the compound of formula (I) equivalent to or higher than that of prior art processes, avoids multi-stage extraction work-up steps for producing crude reaction products, and achieves a higher space-time yield, thus enabling the process of the present invention to be implemented at a lower cost. Avoiding multi-stage extraction work-up steps further reduces the amount of waste that must be incinerated or otherwise disposed of. In the process of the present invention, the compound of formula (I) is isolated in the mixture of the present invention, i.e., in isolated fraction A, in a chemical yield exceeding 95 percent of the theoretical value. In addition, in the process of the present invention, the mass proportion of the compound of formula (I) present in fractions A and B is greater than 99 percent based on the mass of the compound of formula (I) in the crude reaction products used to produce fractions A and B. This confirms that virtually no decomposition of the compound of formula (I) occurs in the process of the present invention. [Examples]

[0071] A. Preparation of crude reaction products Empty, deactivated 2m 3In a Hastelloy C reactor, 125 kg of 100% toluene was charged, and stirring was started at a speed of 60 rpm, followed by heating to 80°C. Next, 250 kg of water and 481.3 kg of 2-piperidineethanol (2-(2-hydroxyethyl)piperidine) (content: 99 wt%, 3.69 kmol) were added. The feed, through which 2-piperidineethanol had been transferred into the reactor, was washed away with 50 kg of toluene. While stirring, 453 kg of 32.0% sodium hydroxide solution (3.62 kmol) and 500 kg of s-butyl chloroformate (content: 99.0 wt%, 3.62 kmol) were added over 6 hours at 85°C, while maintaining the pH between 8.5 and 9.5. The reaction is exothermic, and external cooling is necessary to limit the reaction temperature to 85°C.

[0072] After the reaction was complete, the reaction mixture was cooled to 62°C. 100 kg of 10 percent sulfuric acid (0.102 kmol) was added. The two-phase reaction mixture was stirred for a further 15 minutes. After that, stirring was stopped to allow for phase separation. After phase separation, the lower 948 kg of aqueous phase was withdrawn from the reactor.

[0073] Next, for the first acid washing, 481.2 kg of toluene (100% by weight), 40 kg of water, and 20 kg of 10 percent sulfuric acid (20.4 mol) were added to the organic phase remaining in the reactor. The mixture was heated to 60°C with stirring and stirred for a further 15 minutes. Again, stirring was stopped to allow for phase separation. After phase separation, the lower 57.2 kg of aqueous phase was withdrawn from the reactor.

[0074] 1. Crude reaction product A The 3.299 g of organic phase obtained in this manner was adjusted to a pH of 4.8-6 by adding dilute NaOH, and the aqueous phase was separated and removed. First, the toluene present in it was removed by distillation at 90°C and 80 hPa, and then the organic phase was used as Invention Example 4. 91 g of water was added to the remaining 1.986 g of bottom liquid, and 145 g was removed by distillation at 90°C and 60 hPa. Another 91 g of water was added, and 97 g of the substance was removed by distillation, resulting in a residue of 1.877 g.

[0075] The crude reaction product A obtained in this manner had the following composition.

[0076] [Table 1]

[0077] 2. Crude reaction product B Subsequently, the organic phase remaining after removing 3.299 g to produce crude reaction product A was mixed again with 40.0 kg of water and 20.0 kg of 10 percent sulfuric acid (20.4 mol) for a second acid wash. The mixture was stirred for a further 15 minutes. Again, stirring was stopped to allow for phase separation. After phase separation, the lower 58.5 kg of aqueous phase was withdrawn from the reactor.

[0078] To neutralize the reaction mixture, 125 kg of water was added to the organic phase remaining in the reactor for a third wash. Then, 0.13 kg of 32% sodium hydroxide solution (1 mol) was added to adjust the reaction mixture's pH to 4.8-5.0. The mixture was then stirred for another 10 minutes. Again, stirring was stopped to allow for phase separation. After phase separation, the lower 140.3 kg of aqueous phase was removed from the reactor.

[0079] As a final wash, the organic phase remaining in the reactor was treated with 125 kg of water, where 0.13 kg of 32% sodium hydroxide solution (1 mol) was used to adjust the pH of the mixture to a range of 4.8–7.0 m. The mixture was then stirred for another 10 minutes. Again, stirring was stopped to allow for phase separation. After phase separation, the lower 137.5 kg of aqueous phase was withdrawn.

[0080] The remaining organic phase was removed by distillation using 641.3 kg of toluene solvent at a pressure of 650 hPa and a bottom liquid temperature of up to 90°C. Subsequently, 37.5 kg of water was added, and the mixture was stirred for a further 60 minutes. Then, 40.0 kg of water was removed from the bottom liquid by distillation under conditions of up to 90°C and 60 hPa. Subsequently, the pressure in the reactor was increased to atmospheric pressure using nitrogen, the reactor was cooled to a temperature below 60°C, and the crude mixture was removed from the reactor through a filter.

[0081] 825.0 kg of crude mixture was obtained, which was used as the starting material for the process of the present invention.

[0082] The crude reaction product B obtained in this manner had the following composition.

[0083] [Table 2]

[0084] B. Process for producing a mixture from crude reaction products Example 1 (Non-inventive invention) Initially, 1523 g of crude reaction product B was charged into a 2 L flanged tank equipped with a 10-tray column, a deflegmeter with reflux divider, and a vacuum pump with a cold trap. The system was then evacuated to 20 hPa. The deflegmeter was adjusted to 50°C, and reflux was divided at a reflux ratio of (1:1) (volume ratio of reflux to distillate withdrawal). The system was brought to a boil at an internal temperature of approximately 175°C, but most of the substance condensed in the cold trap. The distillation was then stopped. Approximately 102 g of the substance was present in the cold trap, and approximately 1386 g was present in the bottom liquid. The substance in the cold trap consisted of approximately 99% 2-butanol; the bottom liquid in the flanged tank consisted of approximately 82.3 wt% of compound (I) and 16% of compound (III) (formed by the elimination of butanol from compound (I)). Therefore, it was impossible to obtain the compound of formula (I) as a distillate at 175°C and 20 hPa. Instead, the reaction product decomposed via the elimination of butanol. The residence time of the liquid phase containing the crude reaction product was longer than 60 minutes.

[0085] Example 2 (The present invention) The apparatus used in this example consisted of a thin-film evaporator with an oil-filled jacket (30 cm long, 5 cm inner diameter), three wiper arms with rollers, an internal temperature measuring device at the bottom liquid outlet, a constant-temperature condenser (defleg meter), and a vacuum pump with a cold trap. The evaporator was heated to 150-160°C using oil, and the reduced pressure was adjusted to 2 hPa. The condenser was operated at 50°C using oil. 200-250 g of crude reaction product B was continuously weighed and charged over 1 hour. The wiper speed was 120 rpm. The internal temperature of the thin-film apparatus was between 135°C and 140°C. A total of 5107 g of Saltidin was then weighed and charged. 4869 g of colorless distillate was obtained as fraction A, 130 g of brown liquid bottom liquor was obtained from the thin-film apparatus as fraction B, and 7.1 g of liquid was collected in the cold trap as fraction C. This represents a 98% mass balance. The average residence time of the liquid phase containing the crude reaction products and / or fraction B or various mixtures thereof was less than 60 seconds. The reaction products thus obtained had the properties shown in the following table.

[0086] [Table 3]

[0087] The condensate (condensed fraction C) was collected in a cold trap and contained 97% by weight of water. The brown to dark brown bottom liquor contained approximately 200–500 ppm of sodium chloride and sodium sulfate, in addition to trace amounts of further inorganic components.

[0088] Example 3 (The present invention) The apparatus used in this example consisted of an oil-filled jacketed thin-film evaporator (30 cm long, 5 cm inner diameter), three wiper arms with rollers and an internal temperature gauge at the bottom liquid outlet, a 10-tray mirror-finished tracing-heated column packed with HC4 wire mesh rings (packing length 30 cm, diameter 24 mm, approximately 10 theoretical stages), a reflux divider and a constant-temperature condenser (deflegmeter), and a vacuum pump with a cold trap. The evaporator was heated to 178°C using oil, and the pressure was adjusted to 3 hPa. The insulated column was heated to 164°C by external tracing for insulation. The condenser was operated at 90°C using oil. 60 g of crude reaction product B was continuously weighed and charged between the column and the thin-film evaporator over 1 hour, and refluxed through the reflux divider at a reflux ratio of (1:2) (reflux / withdrawal, volume / volume). The wiper speed was 120 rpm. The internal temperature at the bottom of the thin-film apparatus was between 155 and 160°C. The pressure at the bottom of the column was 5.5 hPa, while a pressure of 3.3 hPa was measured at the top of the column. In this manner, a total of 1715 g of crude reaction product B was metered and charged into the thin-film evaporator. 1687 g of fraction A was obtained as a colorless distillate; 17 g of fraction B was obtained from the thin-film apparatus in the form of a brown liquid bottom liquid; and 3.8 g of fraction C was condensed in the cold trap. This corresponds to a mass balance of over 99% by weight. The average residence time of the liquid phase containing the crude reaction product and / or fraction B or various mixtures thereof was less than 60 seconds. The reaction product thus obtained had the properties shown in the following table.

[0089] [Table 4]

[0090] The condensate (condensed fraction C) was collected in a cold trap and contained 90% by weight of 2-butanol, 1.7% by weight of toluene, 1.1% by weight of Saltidin, and other components. The brown to dark brown bottom liquor contained 76% by weight of Saltidin, 20.1% by weight of the compound of formula (II), and other components.

[0091] Example 4 (The present invention) The apparatus used in this example consisted of an oil-filled jacketed thin-film evaporator (30 cm long, 5 cm inner diameter), three wiper arms with rollers and an internal temperature gauge at the bottom liquid outlet, a 10-tray mirror-finished tracing-heated column packed with HC4 wire mesh rings (packing length 30 cm, diameter 24 mm, approximately 10 theoretical stages), a reflux divider and a constant-temperature condenser (deflegmeter), and a vacuum pump with a cold trap. The evaporator was heated to 178°C using oil, and the pressure was adjusted to 3 hPa. The insulated column was heated to 164°C by external tracing for insulation. The condenser was operated at 90°C using oil. 70 g of crude reaction product A was continuously weighed and charged between the column and the thin-film evaporator over 1 hour, and the reflux ratio (reflux / withdrawal, volume / volume) was set to (1:2) via the reflux divider. The wiper speed was 200 rpm. The internal temperature at the bottom of the thin-film apparatus was between 155 and 160°C. The pressure at the bottom of the column was 7 hPa, while a pressure of 3.0 hPa was measured at the top of the column. A total of 1365 g of Saltidin was then weighed and charged. 1300 g of colorless distillate was obtained, 55 g of brown liquid bottom liquor was obtained from the thin-film apparatus, and 2 g of liquid was collected in a cold trap. This represents a mass balance of over 99%. The average residence time of the liquid phase containing the crude reaction products and / or fraction B or various mixtures thereof was less than 60 seconds. The reaction products thus obtained had the properties shown in the following table.

[0092] [Table 5]

[0093] The condensate (condensed fraction C) was collected in a cold trap and contained 90% by weight of 2-butanol, 1.7% by weight of toluene, 1.1% by weight of Saltidin, and other components. The brown to dark brown bottom liquor contained 76% by weight of Saltidin, 20.1% by weight of the compound of formula (II), and other components.

Claims

1. A mixture, with the following components: Formula for 98.8% to 100.0% by weight, preferably 99.0% to 99.9% by weight (I): 【Chemistry 1】 The compound, 0.00% by weight to 0.60% by weight, preferably 0.0001% by weight to 0.20% by weight Formula (II): 【Chemistry 2】 Compounds of, Further ingredients Includes, The sum of the weight percentages of the aforementioned components is 100% by weight. The mixture has a Hazen color number of 0 to 15 as measured by the DIN EN ISO 6271 method.

2. Formula (III) of the above in amounts from 0.0001% by weight to 2.0% by weight: 【Transformation 3】 The mixture according to claim 1, comprising the compound.

3. A process for producing the mixture described in claim 1 or 2, Starting from a crude reaction product containing 94.0% to 98.0% by weight of the compound of formula (I), At least fraction A (distillate) is obtained from fraction B (bottom liquid) and gas fraction C in the following steps: a) The crude reaction product in liquid phase is subjected to heat treatment, preferably by bringing it into contact with a fixed heating surface, to form a gas stream G containing fractions A and C, and fraction B is left as a liquid phase, and b) Simultaneously and / or subsequently, the step of withdrawing fraction B from the process in a liquid form, c) Simultaneously and / or subsequently, condense fraction A from gas stream G and remove it from the process to obtain the mixture described in claim 1 or 2, and d) In some cases, simultaneously and / or subsequently, fraction C is separated by the step of condensing it and withdrawing it from the process. A process wherein the residence time of the liquid phase during the heat treatment, preferably the residence time of the liquid phase containing the crude reaction product and / or fraction B or various mixtures thereof, is 1 to 900 seconds, preferably 10 to 600 seconds, more preferably 10 to 300 seconds.

4. The process according to claim 3, starting from a crude reaction product having at least 40 Hazen color numbers as measured by the DIN-ISO 6271 method.

5. At least, the following: - Evaporation unit (1), inlet (21) for crude reaction product, and outlet (31) for fraction B: ○Here, the evaporation unit (1) includes at least the following: ○A heatable housing shell enclosing a rotationally symmetric evaporation space extending in the axial direction, and ○In order to form a film of crude reaction products on the inner surface of the housing shell, and A drivable rotor shaft, extending coaxially within the evaporation space, for moving the substance from the inlet (21) for the crude reaction product toward the outlet (31) for fraction B (the rotor shaft has a central rotor shaft body and rotor elements arranged around it, the radially outermost end of which is located slightly away from the inner surface of the housing shell), and, - Condenser (5), reflux divider (6), and outlet (63) for fraction A, Preferably column (4): This is carried out using equipment that includes, ○In step a), The crude reaction product is introduced into the evaporation space of the evaporation unit (1) through the inlet (21), the crude reaction product is subjected to heat treatment, and a liquid film of the crude reaction product is formed on the inside of the housing shell. As a result, the liquid film of the crude reaction product is heated to a temperature at which at least a portion of fractions A and C are converted into a gaseous state and discharged as a gas stream G from the evaporation unit (1), preferably through the outlet (11), where the ratio of the mass flow rate between fraction B and gas stream G is between (1:20) and (1:5). ○In step b), fraction B is discharged from the evaporation unit (1) through the outlet (31), ○In step c), the gas stream G moves from the evaporation unit (1), preferably through the column (4), into the condenser (5), where fraction A is condensed and obtained through the reflux divider (6) and outlet (63). The process according to claim 3 or 4, characterized in that

6. The process according to claim 5, characterized in that it is carried out in an apparatus including a condenser (7) in which fraction C is condensed in step d).

7. The process according to claim 5 or 6, characterized in that the liquid film subjected to heat treatment in the evaporation unit (1) has a film thickness of 0.001 to 2 mm, preferably 0.005 to 1 mm.

8. In step a), fraction A is - A temperature of 120 to 200°C, preferably 120 to 185°C, more preferably 120 to 175°C, and a pressure of 1 to 35 hPa, preferably 1 to 21 hPa, more preferably 2 to 15 hPa, or The process according to any one of claims 3 to 7, wherein fraction A is converted to the gas phase at a temperature 40°C or less higher than its boiling point, preferably 30°C or less higher.

9. The process according to any one of claims 3 to 8, characterized in that no co-retention agent is added to the crude reaction product at any point in the process.

10. i. A step of reacting 2-hydroxyethylpiperidine with sec-butyl chloroformate in the presence or absence of at least one base and at least one solvent to obtain a reaction mixture containing 35% to 65% by weight of the compound of formula (I), ii. Next, optionally, add acid and / or water to the reaction mixture from step i. while mixing to form a two-phase reaction reaction comprising an organic phase and an aqueous phase. iii. Next, optionally, a step of separating the organic phase from the aqueous phase of the reaction mixture from step ii. iv. Next, if applicable, the organic phase from step iii. is washed with an acidic aqueous solution. v. Then, if applicable, a step of drying the organic phase from step iv. vi. Then, optionally, separate at least one solvent from the organic phase from step v. to obtain a crude reaction product. The process according to any one of claims 3 to 9, wherein the crude reaction product is produced by a step including the following:

11. An apparatus comprising at least an evaporation unit (1), a tank (3) for fraction B, a condenser (5), and a pump (8).

12. The apparatus according to claim 11, further comprising a column (4), a connecting conduit (11) between the evaporation unit (1) and the column (4), a reflux divider (6), and a condenser (7).

13. The apparatus according to claim 12, further comprising an inlet (21) for crude reaction products, a connecting conduit (41) between columns (4) and (5), a connecting conduit (51) between condenser (5) and condenser (7), a connecting conduit (61) between condenser (5) and reflux divider (6), a connecting conduit (62) between column (4) and reflux divider (6), an outlet (63) for fraction A, and an outlet (72) for fraction C.

14. A process according to any one of claims 3 to 10 for producing the mixture according to claim 1 or 2, in the apparatus according to any one of claims 11 to 13.

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