Preparation method of (S)-2-aminopropanol

Abstract

The invention discloses a preparation method of (S)-2-aminopropanol. The preparation method comprises the following steps: S1, inputting L-2-aminopropionic acid and an organic solvent tetrahydrofuran into a reaction device; s2, dropwise adding the lithium borohydride tetrahydrofuran solution into the reaction device through a dropwise adding device; s3, inputting an ammonium chloride aqueous solution into the reaction device for quenching excessive lithium borohydride which is not completely reacted; s4, inputting the lower-layer water phase in the reaction device into an extraction device, and inputting an extraction solvent into the extraction device to extract the lower-layer water phase in the extraction device; s5, inputting the organic materials in the reaction device and the extraction device into a first distillation device for distillation; and S6, inputting the residual material distilled by the first distillation device into a second distillation device for rectification to obtain (S)-2-aminopropanol. The preparation time of the product is shortened, and the yield of the prepared product is improved.

Description

Technical Field

[0001] The present invention relates to the field of organic chemical synthesis, and in particular to a method for preparing (S)-2-aminopropanol. Background Art

[0002] (S)-2-Aminopropanol is a key raw material used in the synthesis of levofloxacin, the S-type, levorotatory optical isomer of ofloxacin. It boasts twice the antibacterial activity of ofloxacin and exhibits minimal toxicity and side effects. (S)-2-Aminopropanol is also a key chiral raw material in the synthesis of orforglipron, a popular oral small-molecule weight-loss drug. Therefore, market demand for (S)-2-aminopropanol is expected to increase, leading to increased competition. Furthermore, my country's increasingly stringent safety regulations for chemical production necessitate an urgent need for a method and equipment for the industrialized, continuous preparation of (S)-2-aminopropanol to meet market demands.

[0003] At present, the commonly used synthesis methods of (S)-2-aminopropanol industrial preparation methods are as follows:

[0004] The first synthetic route is as follows:

[0005]

[0006] The specific steps are:

[0007] In the first step, L-2-aminopropionic acid is dissolved in ethanol, thionyl chloride is added dropwise and the reaction is completed, ethanol is removed by vacuum distillation, and the mixture is extracted with ether for multiple times and crystallized at low temperature to obtain L-2-aminopropionic acid ethyl ester hydrochloride.

[0008] In the second step, ethyl L-2-aminopropionate hydrochloride is dissolved in ethanol, and then potassium borohydride aqueous solution is added to complete the reaction, followed by multiple extractions with ethyl acetate. After the extraction solution is decompressed to remove the ethyl acetate solvent, the product (S)-2-aminopropanol is distilled out with a yield of about 63%.

[0009] The disadvantages of this two-step synthesis route are that both the first and second steps generate a large amount of organic mixed solvent, making it difficult to recycle and purify the mixed solvent through distillation. This increases the investment in industrial production equipment and the production cost of (S)-2-aminopropanol. The two-step synthesis also affects the yield of the (S)-2-aminopropanol product, making it less competitive in the market.

[0010] The second synthetic route is as follows:

[0011]

[0012] The specific steps are:

[0013] First, the organic solvent ethylene glycol dimethyl ether, anhydrous zinc chloride, and potassium borohydride were added with stirring to produce zinc borohydride. Then, L-2-aminopropionic acid was added. After the reaction was complete, a 40% aqueous solution of caustic soda flakes was added, stirred for 1 hour, and the layers were separated. The separated aqueous layer was extracted several times with n-butanol. The layers were combined, the solvent was evaporated under reduced pressure, and then the product (S)-2-aminopropanol was distilled out in a yield of approximately 56%.

[0014] The disadvantage of this synthetic route is that, although it uses a one-step reaction, the presence of a large amount of solid potassium chloride in the reaction system affects the binding and dispersion of the reaction raw materials, resulting in a long reaction time that affects the yield of the final product, which is approximately 56%. Multiple extractions with n-butanol in the later stages also produce large amounts of organic mixed solvents, which are difficult to recycle and purify by distillation, increasing the investment in industrial production equipment, resulting in high production costs for (S)-2-aminopropanol and a lack of market competitiveness.

[0015] The third method, reported in the literature, uses (S)-propylene oxide and liquid ammonia as raw materials, catalyzed by a modified ion exchange resin under relatively mild reaction conditions, to synthesize (S)-2-aminopropanol. In this method, (S)-propylene oxide readily polymerizes under the strong alkaline conditions of liquid ammonia, and the primary product is the isomer (S)-1-aminopropanol, making it difficult to separate the products. Summary of the Invention

[0016] The invention provides a preparation method of (S)-2-aminopropanol. The invention shortens the preparation time of the product and improves the yield of the prepared product.

[0017] The technical solutions to the above problems are as follows:

[0018] The preparation method of (S)-2-aminopropanol comprises the following steps:

[0019]

[0020] S1, inputting a protective gas into a reaction apparatus, inputting L-2-aminopropionic acid and an organic solvent, tetrahydrofuran, into the reaction apparatus, turning on a stirring assembly on the reaction apparatus to stir, and cooling the reaction apparatus so that the temperature of the solution in the reaction apparatus is reduced to a first temperature;

[0021] S2, adding the lithium borohydride tetrahydrofuran solution dropwise into the reaction apparatus through a dropping device, heating the reaction apparatus until the temperature of the solution in the reaction apparatus rises to a second temperature and then maintaining the temperature;

[0022] S3, introducing an aqueous ammonium chloride solution into the reaction apparatus to quench the unreacted excess lithium borohydride, and allowing the solution in the reaction apparatus to stand to separate into layers to form a lower aqueous phase and an upper organic material layer;

[0023] S4, supplying a protective gas to the extraction device, supplying the lower aqueous phase in the reaction device to the extraction device, supplying an extraction solvent to the extraction device to extract the lower aqueous phase in the extraction device, and after the extraction is completed, allowing the phase to stand and separate to form a lower layer of wastewater and an upper layer of organic material, and after the separation is completed, discharging the wastewater;

[0024] S5, inputting the organic materials in the reaction device and the extraction device into a first distillation device for distillation to distill out the solvent tetrahydrofuran in the organic materials;

[0025] S6, inputting the remaining material after distillation in the first distillation apparatus into a second distillation apparatus for rectification to obtain (S)-2-aminopropanol.

[0026] In the present invention, a single organic solvent, tetrahydrofuran, is used in the preparation process of the present invention, and the recovered tetrahydrofuran can be recycled after dehydration, avoiding the difficulty of mixed solvent distillation and purification and being unable to be effectively recycled, thereby saving preparation cost. A lithium borohydride tetrahydrofuran solution is used in the preparation process. Since the lithium borohydride reduction activity in the lithium borohydride tetrahydrofuran solution is stronger, the reaction process can be effectively improved, the reaction time is shortened, and the reaction byproducts are effectively reduced to improve the product yield. The chemical properties of lithium borohydride are active and flammable, so the present invention is designed to be under nitrogen protection throughout the process, and nitrogen pressurization is used to circulate the material, avoiding contact with air when the material pump circulates the material, ensuring safety during industrial continuous production. In the preparation process of the present invention, an aqueous ammonium chloride solution is used to quench the unreacted excess lithium borohydride, the water layer is extracted with tetrahydrofuran and an ultrasonic device is used to improve the extraction efficiency. Because a large amount of inorganic salts are dissolved in the water layer, the solubility of the product (S)-2-aminopropanol in water is reduced, making the extraction process easier and more thorough, and improving the product yield.

[0027] In summary, the present invention adopts a one-step preparation method, which can effectively shorten the preparation time of the product, improve the yield of the prepared product, use a single organic solvent, and the solvent can be recycled after treatment to save product preparation costs. It is safe to use and can be continuous and industrial production equipment to adapt to the current fierce market competition. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 Schematic diagram of the preparation method of (S)-2-aminopropanol.

[0029] Symbols in the accompanying drawings:

[0030] Reactor A, first valve 1A, second valve 2A, third valve 3A, fifth valve 5A, sixth valve 6A, seventh valve 7A.

[0031] Extraction container B, eleventh valve 1B, twelfth valve 2B, thirteenth valve 3B, fourteenth valve 4B, fifteenth valve 5B, sixteenth valve 6B, seventeenth valve 7B, eighteenth valve 8B, wastewater discharge valve 9B.

[0032] First still C1, first condenser C2, first receiving tank C3, 19th valve 1C, 20th valve 2C, 21st valve 3C, 25th valve 7C. Second still C4, second condenser C5, second receiving tank C6, transfer pump C7, 22nd valve 4C, 23rd valve 5C, 24th valve 6C, 26th valve 8C.

[0033] High-level storage tank D, eighth valve 1D, ninth valve 2D, tenth valve 3D, flow meter 4D.

[0034] Ultrasonic device E, air extraction unit CQ. DETAILED DESCRIPTION

[0035] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0036] like Figure 1 As shown, the preparation method of (S)-2-aminopropanol of the present invention comprises the following steps:

[0037]

[0038] S1, inputting a protective gas into the reaction device, inputting L-2-aminopropionic acid and an organic solvent tetrahydrofuran into the reaction device, turning on a stirring assembly on the reaction device for stirring, and cooling the reaction device so that the temperature of the solution in the reaction device is reduced to a first temperature. In the present invention, nitrogen (the chemical formula of nitrogen is N2) is preferably used as the protective gas, the first temperature is 0-30°C, and the weight ratio of L-2-aminopropionic acid to tetrahydrofuran is 1:1-10.

[0039] The reaction apparatus includes a jacketed reactor A, a first valve 1A for controlling the input of raw materials into the reactor A, a second valve 2A for controlling the delivery of protective gas into the reactor A, a third valve 3A for controlling the discharge of exhaust gas from the reactor A, and a fifth valve 5A, a sixth valve 6A, and a seventh valve 7A for controlling the output of materials. The first valve 1A, the second valve 2A, and the third valve 3A are respectively installed at the top of the reactor A. One end of the fifth valve 5A is connected to the output end at the bottom of the reactor A. The sixth valve 6A and the seventh valve 7A are connected in parallel to the other end of the fifth valve 5A. The other end of the sixth valve 6A is connected to the first distillation apparatus, and the other end of the seventh valve 7A is connected to the extraction apparatus. In the present invention, the reactor A is provided with a stirring assembly, the second valve 2A is connected to the nitrogen supply unit N2, and the third valve 3A is connected to an external exhaust device.

[0040] S2: adding a lithium borohydride tetrahydrofuran solution dropwise to the reaction apparatus via a dropping device, heating the reaction apparatus until the solution temperature in the reaction apparatus reaches a second temperature, and then maintaining the temperature. In the present invention, the concentration of the lithium borohydride tetrahydrofuran solution is 1-6 mol / L, the molar ratio of L-2-aminopropionic acid to lithium borohydride in the lithium borohydride tetrahydrofuran solution is 1:1.05-3.5, and the second temperature is 20-30°C.

[0041] The dropping device includes a high-level storage tank D, an eighth valve 1D for controlling the input of protective gas into the high-level storage tank D, a ninth valve 2D for controlling the discharge of tail gas in the high-level storage tank D, a tenth valve 3D for controlling the delivery of lithium borohydride tetrahydrofuran solution into the high-level storage tank D, and a flow meter 4D with a valve for controlling the input of lithium borohydride tetrahydrofuran solution into the reaction unit. The eighth valve 1D, the ninth valve 2D, and the tenth valve 3D are respectively connected to the high-level storage tank D, and the high-level storage tank D is also connected to the flow meter 4D, which is connected to the reaction unit. In the present invention, the eighth valve 1D is connected to the nitrogen supply unit N2, and the ninth valve 2D is connected to the external tail gas device.

[0042] S3: introducing an aqueous ammonium chloride solution into the reaction apparatus to quench unreacted excess lithium borohydride, and allowing the solution in the reaction apparatus to stand to separate into layers to form a lower aqueous phase and an upper organic material layer. In the present invention, the concentration of the aqueous ammonium chloride solution is 1-25%, the volume ratio of the lithium borohydride tetrahydrofuran solution to the aqueous ammonium chloride solution is 1:1-5, and the unreacted excess lithium borohydride is the lithium borohydride in the lithium borohydride tetrahydrofuran solution.

[0043] S4, supplying a protective gas to the extraction apparatus, supplying the lower aqueous phase in the reaction apparatus to the extraction apparatus, supplying an extraction solvent to the extraction apparatus, activating an ultrasonic device E to extract the lower aqueous phase in the extraction apparatus, and allowing the extraction to stand and separate into a lower layer of wastewater and an upper layer of organic material. After separation, the wastewater is discharged. In the present invention, the protective gas is preferably supplied to the reaction apparatus, and the pressure of the protective gas presses the lower aqueous phase in the reaction apparatus into the extraction apparatus. The extraction solvent is preferably tetrahydrofuran.

[0044] The extraction device includes a primary extraction device, a first valve assembly, a secondary extraction device, a second valve assembly, and a wastewater discharge valve 9B. The input end of the primary extraction device is connected to the reaction device, the output end of the primary extraction device is connected to the first valve assembly, the first valve assembly is connected to the input end of the secondary extraction device, the output end of the secondary extraction device is connected to the second valve assembly and the wastewater discharge valve 9B respectively, and the second valve assembly is connected to the first distillation device.

[0045] Both the primary extraction device and the secondary extraction device include an extraction vessel B, an eleventh valve 1B, a twelfth valve 2B for controlling the input of protective gas into the extraction vessel B, a thirteenth valve 3B for controlling the input of extraction solvent into the extraction vessel B, a fourteenth valve 4B for controlling the discharge of exhaust gas from the extraction vessel B, and an ultrasonic device E. The eleventh valve 1B, the twelfth valve 2B, the thirteenth valve 3B, and the fourteenth valve 4B are respectively connected to the extraction vessel B, and the ultrasonic device E cooperates with the extraction vessel B. In the present invention, the eleventh valve 1B is connected to the other end of the seventh valve 7A, the twelfth valve 2B is connected to the nitrogen supply unit N2, and the fourteenth valve 4B is connected to an external exhaust device.

[0046] The first valve assembly includes a fifteenth valve 5B, a sixteenth valve 6B, and a seventeenth valve 7B. One end of the fifteenth valve 5B is connected to the output end of the primary extraction device, one end of the sixteenth valve 6B and the seventeenth valve 7B are connected in parallel to the other end of the fifteenth valve 5B, the other end of the sixteenth valve 6B is connected to the secondary extraction device, the other end of the sixteenth valve 6B is connected to the eleventh valve 1B in the secondary extraction device, and the other end of the seventeenth valve 7B is connected to the first distillation device.

[0047] The second valve assembly includes an eighteenth valve 8B, one end of the eighteenth valve 8B is connected to the output end of the secondary extraction device, and the other end of the eighteenth valve 8B is connected to the first distillation device.

[0048] S5: The organic material in the reaction unit and the extraction unit is fed into a first distillation apparatus for distillation to remove the tetrahydrofuran solvent from the organic material. In the present invention, the first distillation apparatus includes a first still pot C1, a nineteenth valve 1C, a twentieth valve 2C, a twenty-first valve 3C, a first condenser C2, and a first receiving tank C3. The nineteenth valve 1C and the twenty-first valve 2C are respectively mounted on the top of the first still pot C1. One end of the twenty-first valve 3C is connected to the output end of the first still pot C1, and the other end of the twenty-first valve 3C is connected to the second distillation apparatus. The twentieth valve 2C is connected to the input end of the first condenser C2, and the output end of the first condenser C2 is connected to the first receiving tank C3.

[0049] In the present invention, the sixth valve 6A, the seventeenth valve 7B, and the eighteenth valve 8B are connected in parallel to the nineteenth valve 1C. In the present invention, the first distillation device also includes a twenty-fifth valve 7C, one end of the twenty-fifth valve 7C is connected to the first receiving tank C3, and the other end of the twenty-fifth valve 7C is connected to the exhaust unit CQ.

[0050] S6, the material remaining after distillation in the first distillation apparatus is input into a second distillation apparatus for rectification to obtain (S)-2-aminopropanol. In the present invention, the second distillation apparatus includes a second still kettle C4, a 22nd valve 4C, a 23rd valve 5C, a 24th valve 6C, a second condenser C5, a second receiving tank C6, and a delivery pump C7, one end of the delivery pump C7 is connected to the other end of the 21st valve 3C, the other end of the delivery pump C7 is connected to the 22nd valve 4C, the 22nd valve 4C and the 23rd valve 5C are respectively installed on the upper part of the second still kettle C4, the 24th valve 6C is connected to the output end of the second still kettle C4, the 23rd valve 5C is connected to the input end of the second condenser C5, and the output end of the second condenser C5 is connected to the second receiving tank C6.

[0051] In the present invention, the second distillation apparatus further comprises a twenty-sixth valve 8C, one end of the twenty-sixth valve 8C is connected to the second receiving tank C6, and the other end of the twenty-sixth valve 8C is connected to the gas extraction unit CQ.

[0052] Example 1

[0053] Open second valve 2A, introduce nitrogen for 10 minutes, then open first valve 1A. Feed 400 kg of tetrahydrofuran and 200 kg (2.25 kmol) of L-2-aminopropionic acid into reactor A through first valve 1A. After the feeding is complete, close first valve 1A. Turn on the stirring assembly on reactor A, and inject icy brine into the jacket to cool reactor A down to a first temperature of 10°C.

[0054] After opening valve 8D and introducing nitrogen into overhead storage tank D for 10 minutes, valve 10D was opened to allow 675 L of a 4 mol / L lithium borohydride tetrahydrofuran solution to enter overhead storage tank D through valve 10D. After the addition was complete, valve 10D was closed. Flowmeter 4D was then opened to begin dropwise addition. After the addition was complete, flowmeter 4D was closed. The icy brine in the jacket of reactor A was released, and steam was introduced into the jacket of reactor A to raise the temperature to a second temperature of 20°C and maintain for 8 hours. After the reaction of the raw L-2-aminopropionic acid was complete as determined by liquid chromatography, the reaction was terminated.

[0055] The first valve 1A was opened, and a 15% aqueous solution of ammonium chloride (700 L) was fed into the reactor A, and then the first valve 1A was closed. The aqueous solution of ammonium chloride was used to quench the residual lithium borohydride. After the feeding was completed, the first valve 1A was closed, and the solution in the reactor A was allowed to stand to separate into a lower aqueous phase and an upper organic material layer.

[0056] The twelfth valve 2B in the primary extraction apparatus was opened to introduce nitrogen into extraction vessel B for 10 minutes. The fifth valve 5A, seventh valve 7A, and eleventh valve 1B were then opened to pressurize the solution in reactor A with nitrogen. The lower aqueous phase was then forced into extraction vessel B through the opened fifth valve 5A, seventh valve 7A, and eleventh valve 1B. After the aqueous phase was fully forced out, the fifth valve 5A, seventh valve 7A, and eleventh valve 1B of the primary extraction apparatus were closed. The thirteenth valve 3B in the primary extraction apparatus was then opened, and 500 L of tetrahydrofuran solvent was introduced into extraction vessel B of the primary extraction apparatus. The thirteenth valve 3B was then closed. The ultrasonic device E in the primary extraction apparatus was then opened to ultrasonically extract the solution in extraction vessel B for 1 hour. The ultrasonic device E was then closed, and the solution was allowed to stand for separation to form a lower aqueous phase and an upper organic material layer. The twelfth valve 2B in the secondary extraction apparatus was opened, and nitrogen was introduced into extraction vessel B of the secondary extraction apparatus for 10 minutes. The fifteenth and sixteenth valves 6B in the primary extraction apparatus, as well as the eleventh valve 1B in the secondary extraction apparatus, were then opened. The aqueous phase in extraction vessel B of the primary extraction apparatus was forced into extraction vessel B of the secondary extraction apparatus using nitrogen pressure. After the aqueous phase was forced out, the twelfth, fifteenth, and sixteenth valves 6B in the primary extraction apparatus were closed, as well as the eleventh valve 1B in the secondary extraction apparatus. The thirteenth valve 3B in the secondary extraction apparatus was then opened, and 500 L of tetrahydrofuran solvent was introduced into extraction vessel B of the secondary extraction apparatus. After this, valve 3B was closed. The ultrasonic device E in the secondary extraction apparatus was then opened to ultrasonically extract the solution in extraction vessel B for 1 hour. After this, ultrasonic device E was closed and the solution was allowed to stand for separation to form a lower aqueous phase and an upper organic material layer. Then, wastewater discharge valve 9B was opened, and the lower aqueous phase was discharged through wastewater discharge valve 9B. After the lower aqueous phase was completely discharged, wastewater discharge valve 9B was closed.

[0057] The second valve 2A, fifth valve 5A, and sixth valve 6A of the reaction unit are opened, as are the twelfth valve 2B, fifteenth valve 5B, and seventeenth valve 7B of the primary extraction unit, the twelfth valve 2B and eighteenth valve 8B of the secondary extraction unit, and the nineteenth valve 1C of the first distillation unit. The organic material in reactor A, the organic material in extraction vessel B of the primary extraction unit, and the organic material in extraction vessel B of the secondary extraction unit are then pressurized by nitrogen into the first distillation unit C1. After the feeding is completed, the previously opened valves are closed. Then, the twenty-fifth valve 7C, the twentieth valve 2C, and the exhaust unit CQ are opened to pump air into the first distillation unit C1 to reduce the pressure within the first distillation unit C1. The first distillation unit C1 is activated to distill the tetrahydrofuran solvent from the organic material. The gaseous tetrahydrofuran distills through the twentieth valve 2C and enters the first condenser C2. The gaseous tetrahydrofuran is condensed and converted into a liquid phase, ultimately entering the first receiving tank C3.

[0058] After distillation in the first still C1 is completed, valve 20 and valve 7C are closed, while valve 3C, transfer pump C7, and valve 4C are opened. Transfer pump C7 then transfers the organic material from the first still C1 to the second still C4. After the feeding is complete, the aforementioned valves are closed, and valve 8C and valve 5C are opened. The vacuum unit CQ then pumps air into the second still C4 to reduce the pressure within. The second still C4 is then activated to distill (S)-2-aminopropanol from the solution. The gaseous (S)-2-aminopropanol enters the second condenser C5 through valve 5C, where it is condensed and converted into a liquid phase. The liquid is then transferred from the second condenser C5 to the second receiving tank C6.

[0059] In this example, 135 kg of (S)-2-aminopropanol was obtained with a yield of 80% and a chemical purity of 99.2% according to gas chromatography analysis.

[0060] Specific rotation [a] 20 D =+18.1° (c=0.5 mol / L, methanol).

[0061] Example 2

[0062] Open second valve 2A, introduce nitrogen for 10 minutes, then open first valve 1A. 500 kg of tetrahydrofuran and 200 kg (2.25 kmol) of L-2-aminopropionic acid are fed into reactor A through first valve 1A. After the feeding is complete, close first valve 1A. The stirring assembly on reactor A is activated, and icy brine is introduced into the jacket to cool reactor A down to a first temperature of 15°C.

[0063] After opening valve 8D to introduce nitrogen into overhead storage tank D for 10 minutes, valve 10D was opened to allow 600 L of a 5 mol / L lithium borohydride tetrahydrofuran solution to enter overhead storage tank D through valve 10D. After the addition was complete, valve 10D was closed. Flowmeter 4D was then opened to begin dropwise addition. After the dropwise addition was complete, flowmeter 4D was closed. The icy brine in the jacket of reactor A was released, and steam was introduced into the jacket of reactor A to raise the temperature of reactor A to a second temperature of 25°C and maintain for 6 hours. After the reaction of the raw L-2-aminopropionic acid was complete as determined by liquid chromatography, the reaction was terminated.

[0064] The first valve 1A was opened, and a 13% aqueous solution of ammonium chloride (750 L) was fed into the reactor A, and then the first valve 1A was closed. The aqueous solution of ammonium chloride was used to quench the residual lithium borohydride. After the feeding was completed, the first valve 1A was closed, and the solution in the reactor A was allowed to stand to separate into a lower aqueous phase and an upper organic material layer.

[0065] The twelfth valve 2B in the primary extraction apparatus was opened to introduce nitrogen into extraction vessel B for 10 minutes. The fifth valve 5A, seventh valve 7A, and eleventh valve 1B were then opened to pressurize the solution in reactor A with nitrogen. The lower aqueous phase was then forced into extraction vessel B through the opened fifth valve 5A, seventh valve 7A, and eleventh valve 1B. After the aqueous phase was fully forced out, the fifth valve 5A, seventh valve 7A, and eleventh valve 1B of the primary extraction apparatus were closed. The thirteenth valve 3B in the primary extraction apparatus was then opened, and 500 L of tetrahydrofuran solvent was introduced into extraction vessel B of the primary extraction apparatus. The thirteenth valve 3B was then closed. The ultrasonic device E in the primary extraction apparatus was then opened to ultrasonically extract the solution in extraction vessel B for 1 hour. The ultrasonic device E was then closed, and the solution was allowed to stand for separation to form a lower aqueous phase and an upper organic material layer. The twelfth valve 2B in the secondary extraction apparatus was opened, and nitrogen was introduced into extraction vessel B of the secondary extraction apparatus for 10 minutes. The fifteenth and sixteenth valves 6B in the primary extraction apparatus, as well as the eleventh valve 1B in the secondary extraction apparatus, were then opened. The aqueous phase in extraction vessel B of the primary extraction apparatus was forced into extraction vessel B of the secondary extraction apparatus using nitrogen pressure. After the aqueous phase was forced out, the twelfth, fifteenth, and sixteenth valves 6B in the primary extraction apparatus were closed, as well as the eleventh valve 1B in the secondary extraction apparatus. The thirteenth valve 3B in the secondary extraction apparatus was then opened, and 500 L of tetrahydrofuran solvent was introduced into extraction vessel B of the secondary extraction apparatus. After this, valve 3B was closed. The ultrasonic device E in the secondary extraction apparatus was then opened to ultrasonically extract the solution in extraction vessel B for 1 hour. After this, ultrasonic device E was closed and the solution was allowed to stand for separation to form a lower aqueous phase and an upper organic material layer. Then, wastewater discharge valve 9B was opened, and the lower aqueous phase was discharged through wastewater discharge valve 9B. After the lower aqueous phase was completely discharged, wastewater discharge valve 9B was closed.

[0066] The second valve 2A, fifth valve 5A, and sixth valve 6A of the reaction unit are opened, as are the twelfth valve 2B, fifteenth valve 5B, and seventeenth valve 7B of the primary extraction unit, the twelfth valve 2B and eighteenth valve 8B of the secondary extraction unit, and the nineteenth valve 1C of the first distillation unit. The organic material in reactor A, the organic material in extraction vessel B of the primary extraction unit, and the organic material in extraction vessel B of the secondary extraction unit are then pressurized by nitrogen into the first distillation unit C1. After the feeding is completed, the previously opened valves are closed. Then, the twenty-fifth valve 7C and the twentieth valve 2C are opened, and the vacuum unit CQ is used to pump air into the first distillation unit C1 to reduce the pressure within the first distillation unit C1. The first distillation unit C1 is activated to distill the tetrahydrofuran solvent from the organic material. The vaporous tetrahydrofuran distills through the twentieth valve 2C and enters the first condenser C2. The vaporous tetrahydrofuran is condensed and converted to a liquid phase, ultimately entering the first receiving tank C3.

[0067] After distillation in the first still C1 is completed, valve 20 and valve 7C are closed, while valve 3C, transfer pump C7, and valve 4C are opened. Transfer pump C7 then transfers the organic material from the first still C1 to the second still C4. After the feeding is complete, the aforementioned valves are closed, valve 8C and valve 5C are opened, and the vacuum unit CQ operates to pump air into the second still C4 to reduce the pressure within. The second still C4 is then activated to distill (S)-2-aminopropanol from the solution. The gaseous (S)-2-aminopropanol enters the second condenser C5 through valve 5C, where it is condensed and converted into a liquid phase. The liquid is then transferred from the second condenser C5 to the second receiving tank C6.

[0068] In this example, 138.4 kg of (S)-2-aminopropanol was obtained with a yield of 82% and a chemical purity of 99.1% according to gas chromatography analysis.

[0069] Specific rotation [a] 20 D =+18.2° (c=0.5 mol / L, methanol).

[0070] Example 3

[0071] Open second valve 2A, introduce nitrogen for 10 minutes, then open first valve 1A. 500 kg of tetrahydrofuran and 200 kg (2.25 kmol) of L-2-aminopropionic acid are fed into reactor A through first valve 1A. After the feeding is complete, close first valve 1A. The stirring assembly on reactor A is activated, and icy brine is introduced into the jacket to cool reactor A down to a first temperature of 15°C.

[0072] After opening valve 8D and introducing nitrogen into overhead storage tank D for 10 minutes, valve 10D was opened to allow 675 L of a 4 mol / L lithium borohydride tetrahydrofuran solution to enter overhead storage tank D through valve 10D. After the addition was complete, valve 10D was closed. Flowmeter 4D was then opened to begin dropwise addition. After the addition was complete, flowmeter 4D was closed. The icy brine in the jacket of reactor A was released, and steam was introduced into the jacket of reactor A to raise the temperature to a second temperature of 30°C and maintain for 8 hours. After the reaction of the raw L-2-aminopropionic acid was complete as determined by liquid chromatography, the reaction was terminated.

[0073] The first valve 1A was opened, and a 10% aqueous solution of ammonium chloride (800 L) was fed into the reactor A, and then the first valve 1A was closed. The aqueous solution of ammonium chloride was used to quench the residual lithium borohydride. After the feeding was completed, the first valve 1A was closed, and the solution in the reactor A was allowed to stand to separate into a lower aqueous phase and an upper organic material layer.

[0074] The twelfth valve 2B in the primary extraction apparatus was opened to introduce nitrogen into extraction vessel B for 10 minutes. The fifth valve 5A, seventh valve 7A, and eleventh valve 1B were then opened to pressurize the solution in reactor A with nitrogen. The lower aqueous phase was then forced into extraction vessel B through the opened fifth valve 5A, seventh valve 7A, and eleventh valve 1B. After the aqueous phase was fully forced out, the fifth valve 5A, seventh valve 7A, and eleventh valve 1B of the primary extraction apparatus were closed. The thirteenth valve 3B in the primary extraction apparatus was then opened, and 500 L of tetrahydrofuran solvent was introduced into extraction vessel B of the primary extraction apparatus. The thirteenth valve 3B was then closed. The ultrasonic device E in the primary extraction apparatus was then opened to ultrasonically extract the solution in extraction vessel B for 1 hour. The ultrasonic device E was then closed, and the solution was allowed to stand for separation to form a lower aqueous phase and an upper organic material layer. The twelfth valve 2B in the secondary extraction apparatus was opened, and nitrogen was introduced into extraction vessel B of the secondary extraction apparatus for 10 minutes. The fifteenth and sixteenth valves 6B in the primary extraction apparatus, as well as the eleventh valve 1B in the secondary extraction apparatus, were then opened. The aqueous phase in extraction vessel B of the primary extraction apparatus was forced into extraction vessel B of the secondary extraction apparatus using nitrogen pressure. After the aqueous phase was forced out, the twelfth, fifteenth, and sixteenth valves 6B in the primary extraction apparatus were closed, as well as the eleventh valve 1B in the secondary extraction apparatus. The thirteenth valve 3B in the secondary extraction apparatus was then opened, and 500 L of tetrahydrofuran solvent was introduced into extraction vessel B of the secondary extraction apparatus. After this, valve 3B was closed. The ultrasonic device E in the secondary extraction apparatus was then opened to ultrasonically extract the solution in extraction vessel B for 1 hour. After this, ultrasonic device E was closed and the solution was allowed to stand for separation to form a lower aqueous phase and an upper organic material layer. Then, wastewater discharge valve 9B was opened, and the lower aqueous phase was discharged through wastewater discharge valve 9B. After the lower aqueous phase was completely discharged, wastewater discharge valve 9B was closed.

[0075] The second valve 2A, fifth valve 5A, and sixth valve 6A of the reaction unit are opened, as are the twelfth valve 2B, fifteenth valve 5B, and seventeenth valve 7B of the primary extraction unit, the twelfth valve 2B and eighteenth valve 8B of the secondary extraction unit, and the nineteenth valve 1C of the first distillation unit. The organic material in reactor A, the organic material in extraction vessel B of the primary extraction unit, and the organic material in extraction vessel B of the secondary extraction unit are pressurized by nitrogen into the first distillation unit C1. After the feeding is completed, the previously opened valves are closed. Then, the twenty-fifth valve 7C and the twentieth valve 2C are opened, and the vacuum unit CQ operates to pump air into the first distillation unit C1 to reduce the pressure within the unit. The first distillation unit C1 is activated to distill the tetrahydrofuran solvent from the organic material. The vaporous tetrahydrofuran distills through the twentieth valve 2C and enters the first condenser C2. The vaporous tetrahydrofuran is condensed and converted to a liquid phase, ultimately entering the first receiving tank C3.

[0076] After distillation in the first still C1 is completed, valve 20 and valve 7C are closed, while valve 3C, transfer pump C7, and valve 4C are opened. Transfer pump C7 then transfers the organic material from the first still C1 to the second still C4. After the feeding is complete, the aforementioned valves are closed, valve 8C and valve 5C are opened, and the vacuum unit CQ operates to pump air into the second still C4 to reduce the pressure within. The second still C4 is then activated to distill (S)-2-aminopropanol from the solution. The gaseous (S)-2-aminopropanol enters the second condenser C5 through valve 5C, where it is condensed and converted into a liquid phase. The liquid is then transferred from the second condenser C5 to the second receiving tank C6.

[0077] In this example, 142 kg of (S)-2-aminopropanol was obtained with a yield of 84% and a chemical purity of 99.22% according to gas chromatography analysis.

[0078] Specific rotation [a] 20 D =+18.1° (c=0.5 mol / L, methanol).

Claims

1. A method for preparing (S)-2-aminopropanol, characterized in that: The following steps are involved: S1, inputting a protective gas into a reaction apparatus, inputting L-2-aminopropionic acid and an organic solvent, tetrahydrofuran, into the reaction apparatus, turning on a stirring assembly on the reaction apparatus to stir, and cooling the reaction apparatus so that the temperature of the solution in the reaction apparatus is reduced to a first temperature; S2, adding the lithium borohydride tetrahydrofuran solution dropwise into the reaction apparatus through a dropping device, heating the reaction apparatus until the temperature of the solution in the reaction apparatus rises to a second temperature and then maintaining the temperature; S3, introducing an aqueous ammonium chloride solution into the reaction apparatus to quench the unreacted excess lithium borohydride, and allowing the solution in the reaction apparatus to stand to separate into layers to form a lower aqueous phase and an upper organic material layer; S4, supplying a protective gas to the extraction device, supplying the lower aqueous phase in the reaction device to the extraction device, supplying an extraction solvent to the extraction device to extract the lower aqueous phase in the extraction device, and after the extraction is completed, allowing the phase to stand and separate to form a lower layer of wastewater and an upper layer of organic material, and after the separation is completed, discharging the wastewater; S5, inputting the organic materials in the reaction device and the extraction device into a first distillation device for distillation to distill out the solvent tetrahydrofuran in the organic materials; S6, inputting the remaining material after distillation in the first distillation apparatus into a second distillation apparatus for rectification to obtain (S)-2-aminopropanol.

2. The method for preparing (S)-2-aminopropanol according to claim 1, wherein The reaction device comprises a reactor (A) with a jacket, a first valve (1A) for controlling the input of raw materials into the reactor (A), a second valve (2A) for controlling the delivery of protective gas into the reactor (A), a third valve (3A) for controlling the discharge of tail gas in the reactor (A), a fifth valve (5A), a sixth valve (6A), and a seventh valve (7A) for controlling the output of materials; The first valve (1A), the second valve (2A), and the third valve (3A) are respectively installed on the upper part of the reaction kettle (A); one end of the fifth valve (5A) is connected to the output end at the bottom of the reaction kettle (A); the sixth valve (6A) and the seventh valve (7A) are connected in parallel to the other end of the fifth valve (5A); the other end of the sixth valve (6A) is connected to the first distillation device, and the other end of the seventh valve (7A) is connected to the extraction device.

3. The preparation method of (S)-2-aminopropanol according to claim 1, wherein The dropping device comprises a high-level storage tank (D), an eighth valve (1D) for controlling the input of protective gas into the high-level storage tank (D), a ninth valve (2D) for controlling the discharge of tail gas in the high-level storage tank (D), a tenth valve (3D) for controlling the delivery of lithium borohydride tetrahydrofuran solution into the high-level storage tank (D), and a flow meter (4D) with a valve for controlling the input of lithium borohydride tetrahydrofuran solution into a reaction device. The eighth valve (1D), the ninth valve (2D), and the tenth valve (3D) are respectively connected to the high-level storage tank (D), the high-level storage tank (D) is also connected to the flow meter (4D), and the flow meter (4D) is connected to the reaction device.

4. The method for preparing (S)-2-aminopropanol according to claim 1, wherein The extraction device includes a primary extraction device, a first valve assembly, a secondary extraction device, a second valve assembly, and a wastewater discharge valve (9B). The input end of the primary extraction device is connected to the reaction device, the output end of the primary extraction device is connected to the first valve assembly, the first valve assembly is connected to the input end of the secondary extraction device, the output end of the secondary extraction device is respectively connected to the second valve assembly and the wastewater discharge valve (9B), and the second valve assembly is connected to the first distillation device.

5. The method for preparing (S)-2-aminopropanol according to claim 4, wherein The primary extraction device and the secondary extraction device both comprise an extraction container (B), an eleventh valve (1B), a twelfth valve (2B) for controlling the input of protective gas into the extraction container (B), a thirteenth valve (3B) for controlling the input of extraction solvent into the extraction container (B), a fourteenth valve (4B) for controlling the discharge of tail gas from the extraction container (B), and an ultrasonic device (E). The eleventh valve (1B), the twelfth valve (2B), the thirteenth valve (3B), and the fourteenth valve (4B) are respectively connected to the extraction container (B), and the ultrasonic device (E) cooperates with the extraction container (B).

6. The method for preparing (S)-2-aminopropanol according to claim 4, wherein The first valve assembly includes a fifteenth valve (5B), a sixteenth valve (6B), and a seventeenth valve (7B), one end of the fifteenth valve (5B) is connected to the output end of the primary extraction device, one end of the sixteenth valve (6B) and the seventeenth valve (7B) are connected in parallel to the other end of the fifteenth valve (5B), the other end of the sixteenth valve (6B) is connected to the secondary extraction device, and the other end of the seventeenth valve (7B) is connected to the first distillation device; The second valve assembly comprises an eighteenth valve (8B), one end of the eighteenth valve (8B) is connected to the output end of the secondary extraction device, and the other end of the eighteenth valve (8B) is connected to the first distillation device.

7. The method for preparing (S)-2-aminopropanol according to claim 1, wherein The first temperature is 0-30°C.

8. The method for preparing (S)-2-aminopropanol according to claim 1, wherein The concentration of the lithium borohydride tetrahydrofuran solution is 1-6 mol / L.

9. The method for preparing (S)-2-aminopropanol according to claim 1, wherein The concentration of the ammonium chloride aqueous solution is 1-25%.

10. The method for preparing (S)-2-aminopropanol according to claim 1, wherein The weight ratio of L-2-aminopropionic acid to tetrahydrofuran is 1:1-10; The molar ratio of L-2-aminopropionic acid to lithium borohydride in lithium borohydride tetrahydrofuran solution is 1:1.05-3.5; The volume ratio of the lithium borohydride tetrahydrofuran solution to the ammonium chloride aqueous solution is 1:1-5.

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