Process for recovering hydroxypropyl tetrahydropyrantriol from mother liquor

Abstract

The invention relates to a process for recovering hydroxypropyl tetrahydropyrantriol from a hydroxypropyl tetrahydropyrantriol crystallization mother liquor. The process comprises the following steps: carrying out vacuum concentration on mother liquor until the mother liquor is dry, adding an organic solvent I into concentrate to completely dissolve the concentrate, filtering, adding activated carbon into filtrate, heating, decoloring, re-filtering, feeding an organic solvent II into filtrate II, growing crystals, and cooling, feeding an organic solvent II for the second time, cooling, and growing grains again; and filtering the material after crystal growing, washing a filter cake, and drying to obtain a crude product of hydroxypropyl tetrahydropyrantriol. By adopting the method disclosed by the invention, the crude product of the hydroxypropyl tetrahydropyrantriol with the content up to 88.2% and the yield up to 70.4% can be obtained, the loss of the hydroxypropyl tetrahydropyrantriol in the enzymatic preparation process is avoided as much as possible, and the yield of the product is improved.

Description

Technical Field

[0001] The present application relates to a process for recovering hydroxypropyl tetrahydropyrantriol from hydroxypropyl tetrahydropyrantriol crystallization mother liquor. Background Art

[0002] Hydroxypropyl tetrahydropyrantriol, also known as benzoin, is a xylose derivative with anti-aging active ingredients. It can promote the production of skin collagen and glycosaminoglycans and improve skin structure to achieve anti-aging effects. It has mild and stable properties and is considered to be one of the three "anti-aging giants" of cosmetic raw materials. Therefore, it plays an important role in the fields of medical beauty and cosmetics and has broad market prospects.

[0003] At present, the industrial preparation methods of hydroxypropyl tetrahydropyrantriol are: chemical synthesis method and biological method. There are documents that disclose the preparation method of hydroxypropyl tetrahydropyrantriol, which uses D-xylose and acetylacetone as raw materials, and performs a reduction reaction under the action of sodium borohydride to obtain hydroxypropyl tetrahydropyrantriol. This method has the risk of introducing inorganic impurities such as borates, and at the same time, the production process has high requirements for production safety and environmental safety.

[0004] There are also literature reports on a method for preparing hydroxypropyl tetrahydropyrantriol by reduction reaction under the action of a catalyst. However, the use of the catalyst leads to a relatively high production cost of hydroxypropyl tetrahydropyrantriol.

[0005] There are also documents that disclose the preparation of hydroxypropyl tetrahydropyrantriol by reducing D-xylopyranosyl-2-(S)acetone under the action of formate dehydrogenase, glucose dehydrogenase or alcohol dehydrogenase. This biological method is safer and more environmentally friendly than the chemical synthesis method, but the subsequent separation and purification steps are cumbersome, the crystallization yield is low, and the mother liquor recovery is difficult, resulting in a lack of obvious cost advantage.

[0006] In recent years, with the continuous breakthroughs in biotechnology, biomanufacturing will become one of the most competitive tracks. How to make full use of the mother liquor of hydroxypropyl tetrahydropyrantriol crystallization synthesized by enzymatic method, improve product yield and reduce production costs has become an urgent problem to be solved in various productions. At present, there are few treatment processes for recovering hydroxypropyl tetrahydropyrantriol from the mother liquor of hydroxypropyl tetrahydropyrantriol crystallization. Summary of the invention

[0007] In order to solve the above technical problems, the present invention provides a process for recovering hydroxypropyl tetrahydropyrantriol from the crystallization mother liquor prepared by enzymatic method as raw material, avoiding the loss of hydroxypropyl tetrahydropyrantriol as much as possible in production and improving the yield of hydroxypropyl tetrahydropyrantriol.

[0008] The process for recovering hydroxypropyl tetrahydropyrantriol from a mother liquor comprises the following steps: (1) Using the hydroxypropyl tetrahydropyrantriol crystallization mother liquor produced in the process of enzymatic synthesis of hydroxypropyl tetrahydropyrantriol as a raw material, the mother liquor is vacuum concentrated to dryness to obtain a concentrate, which is a caramel-colored viscous substance; (2) adding an organic solvent I to the concentrate to completely dissolve the concentrate, filtering, removing insoluble matter, and obtaining a filtrate I, and adding or not adding purified water to the filtrate I; (3) Adding activated carbon, heating, decolorizing, filtering, and obtaining filtrate II; (4) adding organic solvent II to the filtrate II, growing crystals, and cooling; adding organic solvent II a second time, cooling, and growing crystals again; (5) Filter the material after crystallization in (4), wash the filter cake obtained after filtration, and dry it to obtain a crude product of hydroxypropyltetrahydropyrantriol.

[0009] Preferably, the above-mentioned process for recovering hydroxypropyl tetrahydropyrantriol from the mother liquor comprises the following steps: (1) Using the hydroxypropyl tetrahydropyrantriol crystallization mother liquor produced in the process of synthesizing hydroxypropyl tetrahydropyrantriol by an enzymatic method as a raw material, concentrating at 30° C. to 60° C. and a vacuum degree of -0.09 to -0.1 MPa until no condensate is distilled out to obtain a concentrate; (2) adding an organic solvent I to the concentrate to completely dissolve the concentrate, filtering, removing insoluble matter, and obtaining a filtrate I, and adding or not adding purified water to the filtrate I; The organic solvent I is selected from at least one of methanol, ethanol, acetonitrile or isopropanol; the volume mass ratio of the organic solvent I added to the hydroxypropyl tetrahydropyrantriol contained in the mother liquor is (0.9-1.5) mL:1 g, and after dissolution, the impurities insoluble in the organic solvent I are removed by filtration; the organic solvent I is a polar solvent; The amount of purified water used is 0-5% of the volume of organic solvent I; (3) Add activated carbon, heat to 35°C to 50°C, decolorize, and filter to obtain filtrate II; The mass volume ratio of activated carbon added to filtrate I is (1-4) g: 100 mL; (4) Adding organic solvent II to the filtrate at 30-50°C in one go, and completing the addition within 1-3 hours. After growing the crystals for 1.5-3 hours, cool the mixture at a rate of 4-6°C / h. Then, the organic solvent II is added for a second time at 20-40°C for 2-3 hours, and the temperature is lowered to 4-10°C at a rate of 2-6°C / h, and the crystal is grown for 1-3 hours; The organic solvent II is selected from any one or more of ethyl acetate, acetone, butyl acetate, ethyl ether, and methyl tert-butyl ether; the organic solvent II is a non-polar solvent; The volume ratio of the organic solvent II added once to the organic solvent I is 0.5-1:1, and the volume ratio of the organic solvent II added twice to the organic solvent I is 1-2:1; (5) growing crystals, filtering, washing the resulting filter cake with an organic solvent II, and drying to obtain a crude product of hydroxypropyltetrahydropyrantriol.

[0010] The beneficial effects of the present invention are: (1) By adopting the method of the present invention, a crude hydroxypropyl tetrahydropyrantriol product with a content of up to 88.2% and a yield of up to 70.4% can be obtained, thereby avoiding the loss of hydroxypropyl tetrahydropyrantriol during the enzymatic preparation process as much as possible and improving the yield of the product; (2) The crystallization preparation method of the present invention can obtain a solid with a single (β, S) configuration, and the biological activity of the single spatial configuration is higher than that of the mixed configurations of (β, S) and (β, R).

[0011] Hydroxypropyl tetrahydropyrantriol mainly exists in two diastereoisomers, (β, S) and (β, R). The biological activity of a single spatial configuration is higher than that of a mixed configuration. The preparation methods of hydroxypropyl tetrahydropyrantriol reported in the literature mainly obtain a mixed configuration of (β, S) and (β, R). Therefore, the biological activity of the product prepared by the present invention is higher than that of ordinary products. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 A flow chart for recovering hydroxypropyl tetrahydropyrantriol; Figure 2 It is a connection diagram of equipment for recovering hydroxypropyl tetrahydropyrantriol; Figure 2 In the middle, 1-concentration tank, 2-decolorization tank, 3-precision filter, 4-crystallization tank, 5-filter, 6-dryer; Figure 3 The crude product HPLC spectrum of hydroxypropyl tetrahydropyrantriol in Example 1; Figure 4 The crude product HPLC spectrum of hydroxypropyl tetrahydropyrantriol in Example 2; Figure 5 The crude product HPLC spectrum of hydroxypropyl tetrahydropyrantriol in Example 3; Figure 6 The crude product HPLC spectrum of hydroxypropyl tetrahydropyrantriol in Example 4; Figure 7 The crude product HPLC spectrum of hydroxypropyl tetrahydropyrantriol in Example 5; Figure 8 The crude product HPLC spectrum of hydroxypropyl tetrahydropyrantriol in Example 6; Fig. 9HPLC spectrum of crude hydroxypropyl tetrahydropyrantriol in Example 7; Fig.10 This is the HPLC spectrum of the crude hydroxypropyl tetrahydropyrantriol in Example 8. DETAILED DESCRIPTION

[0013] In order to enable those skilled in the art to better understand the present invention, the present invention is further described in conjunction with specific implementation methods.

[0014] Example 1 (1) 500 ml of the hydroxypropyl tetrahydropyrantriol crystallization mother liquor was vacuum concentrated. The hydroxypropyl tetrahydropyrantriol content in the mother liquor was 64% after testing. The mother liquor was concentrated to dryness at 55°C and -0.095 MPa to obtain 310.8 g of a caramel-colored viscous substance. The above mother liquor is obtained in the following enzymatic method for preparing hydroxypropyl tetrahydropyrantriol: using an enzymatic process with β-acetone xyloside as a substrate, reducing and synthesizing (s)-configuration hydroxypropyl tetrahydropyrantriol under the action of carbonyl reductase, and obtaining hydroxypropyl tetrahydropyrantriol crystal mother liquor through microfiltration, ultrafiltration, concentration, and crystallization; the preparation of the mother liquor does not belong to the important protection content of the present invention, and its acquisition process is briefly summarized here; (2) Add 230 ml of methanol to the concentrate, stir to completely dissolve the product, filter to remove impurities insoluble in methanol, add 10 ml of purified water to the filtrate, and mix well; (3) Add 7.8 g of activated carbon, stir and heat to 35°C, decolorize for 1 hour, and filter to obtain a decolorized solution; (4) Stir and heat the decolorizing solution to 40°C, and start to add 173 ml of acetone solvent for crystallization. After 2 hours of addition, keep the temperature at room temperature for 2 hours, then cool it down to 25°C at a rate of 5°C / h, continue to add 402 ml of acetone solvent, and after 2 hours of addition, control the cooling rate of 4°C / h to 6°C, and keep the temperature at room temperature for 2 hours; (5) Filter, add 23 ml of acetone to the filter cake to wash and remove impurities, collect the crystals, and vacuum dry at 45°C to obtain crude hydroxypropyltetrahydropyrantriol.

[0015] After testing, the crude product content of hydroxypropyl tetrahydropyrantriol was 88.2% and the yield was 70.4%.

[0016] The HPLC detection conditions are as follows: Chromatographic column: ADME column; Column temperature: 35 °C; Mobile phase: 10% formic acid solution; Flow rate: 1.0 mL / min; Detector: differential detector, detection cell temperature 40 ℃.

[0017] In the above process, the connection relationship of the whole set of production equipment used is as follows (see attached Figure 2 shown): The concentration tank 1 has a crystallization mother liquor inlet at the top and a concentrated liquid outlet at the bottom. The outlet of the concentration tank 1 is connected to the decolorization tank 2 through a pipeline. The pipeline is also provided with a polar solvent (organic solvent I) inlet and an activated carbon inlet, which are used to transport the organic solvent I and activated carbon to the concentration tank respectively.

[0018] The outlet of the decolorizing tank 2 is connected to the precision filter 3, and the outlet end of the precision filter 3 is connected to the inlet of the crystallization tank 4 through a pipeline. The pipeline is also provided with a purified water inlet and two non-polar solvent inlets (organic solvent II), which respectively transport two different batches of organic solvent II, as shown in the attached figure (0.5-1 times the volume of the polar solvent, 1-2 times the volume of the polar solvent); The pipeline connected to the bottom of the crystallization tank 4 leads to the filter 5, and the pipeline is also connected to the pipeline of the washing liquid. After the crystallized material enters the filter 5, the washing liquid pipeline transports the washing liquid to the filter 5 to rinse the filter cake obtained after filtration, and the waste liquid is discharged through the pipeline at the bottom of the filter 5; The crystals obtained after the crystallization are dried by a dryer 6 to finally obtain a crude product of hydroxypropyltetrahydropyrantriol.

[0019] Example 2 (1) 500 ml of the hydroxypropyl tetrahydropyrantriol crystallization mother liquor was vacuum concentrated. The hydroxypropyl tetrahydropyrantriol content in the mother liquor was 57%. The mother liquor was concentrated to dryness at 60°C and -0.096 MPa to obtain 375.0 g of a caramel-colored viscous substance. (2) Add 300 ml of isopropanol to the concentrate, stir to completely dissolve the product, filter to remove impurities insoluble in isopropanol, add 8 ml of purified water to the filtrate, and mix well; (3) Add 20.2 g of activated carbon, stir and heat to 35°C, decolorize for 1 hour, filter and obtain a decolorized solution; (4) Stir and heat the decolorizing solution to 40°C, and start to add 150 ml of acetone solvent for crystallization. After adding for 3 hours, keep the temperature at room temperature for 2 hours, then cool it down to 25°C at a rate of 5°C / h, continue to add 480 ml of acetone solvent, and after adding for 3 hours, control the cooling rate of 5°C / h to 6°C, and keep the temperature at room temperature for 2 hours; (5) Filter, add 28 ml of acetone to the filter cake to wash and remove impurities, collect the crystals, and dry them in vacuum at 45°C.

[0020] After testing, the crude product content of hydroxypropyl tetrahydropyrantriol was 87.9% and the yield was 73.9%.

[0021] Example 3 (1) 500 ml of the hydroxypropyl tetrahydropyrantriol crystallization mother liquor was vacuum concentrated. The hydroxypropyl tetrahydropyrantriol content in the mother liquor was 52%. The mother liquor was concentrated to dryness at 60°C and -0.096 MPa to obtain 337.6 g of a caramel-colored viscous substance. (2) Add 260 ml of isopropanol to the concentrate, stir to completely dissolve the product, filter to remove impurities insoluble in isopropanol, add 7.8 ml of purified water to the filtrate, and mix well; (3) Add 18.0 g of activated carbon, stir and heat to 40°C, decolorize for 1 hour, and filter to obtain a decolorized solution; (4) Stir and heat the decolorizing solution to 40°C, and start to add 150 ml of ethyl acetate solvent for crystallization. After adding for 3 hours, keep the temperature at room temperature for 2 hours, then cool the temperature to 25°C at a rate of 5°C / h, continue to add 364 ml of ethyl acetate solvent, and after adding for 3 hours, control the cooling rate to 6°C at 5°C / h, and keep the temperature at room temperature for 2 hours; (5) Filter, add 26 ml of acetone to the filter cake to wash and remove impurities, collect the crystals, and dry them in a vacuum at 45°C.

[0022] After testing, the crude product content of hydroxypropyl tetrahydropyrantriol was 86.5% and the yield was 63.1%.

[0023] Example 4 (1) 500 ml of the hydroxypropyl tetrahydropyrantriol crystallization mother liquor was vacuum concentrated. The hydroxypropyl tetrahydropyrantriol content in the mother liquor was 54%. The mother liquor was concentrated to dryness at 60°C and -0.099 MPa to obtain 349.6 g of a caramel-colored viscous substance. (2) Add 290 ml of ethanol to the concentrate, stir to completely dissolve the product, filter to remove impurities insoluble in ethanol, add 7.5 ml of purified water to the filtrate, and mix well; (3) Add 19.5 g of activated carbon, stir and heat to 38°C, decolorize for 1 hour, filter and obtain a decolorized solution; (4) Stir and heat the decolorizing solution to 43°C, and start to add 290 ml of acetone solvent for crystallization. After 3 hours of addition, keep the temperature for 2 hours, then cool it down to 30°C at a rate of 5°C / h, continue to add 290 ml of acetone solvent, and after 3 hours of addition, control the cooling rate to 6°C / h to reduce the temperature to 6°C, and keep the temperature for 3 hours; (5) Filter, add 20 ml of acetone to the filter cake to wash and remove impurities, collect the crystals, and dry them in a vacuum at 45°C.

[0024] After testing, the crude product content of hydroxypropyl tetrahydropyrantriol was 86.4% and the yield was 65.8%.

[0025] Example 5 (1) 500 ml of the hydroxypropyl tetrahydropyrantriol crystallization mother liquor was concentrated under vacuum. The hydroxypropyl tetrahydropyrantriol content in the mother liquor was 52%. The mother liquor was concentrated to dryness at 60°C and -0.099 MPa to obtain 335.7 g of a caramel-colored viscous substance. (2) Add 260 ml of ethanol to the concentrate, stir to completely dissolve the product, filter to remove impurities insoluble in ethanol, add 9.7 ml of purified water to the filtrate, and mix well; (3) Add 19.5 g of activated carbon, stir and heat to 40°C, decolorize for 1 hour, and filter to obtain a decolorized solution; (4) Stir and heat the decolorizing solution to 40°C, and start to add 150 ml of ethyl acetate solvent for crystallization. After adding for 3 hours, keep the temperature at room temperature for 2 hours, then cool the temperature to 30°C at a rate of 5°C / h, continue to add 364 ml of ethyl acetate solvent, and after adding for 3 hours, control the cooling rate to 6°C at 5°C / h, and keep the temperature at room temperature for 3 hours; (5) Filter, add 26 ml of ethyl acetate to the filter cake to wash and remove impurities, collect the crystals, and dry them in vacuo at 45°C.

[0026] After testing, the crude product content of hydroxypropyl tetrahydropyrantriol was 85.2% and the yield was 60.8%.

[0027] Example 6 (1) 500 ml of the hydroxypropyl tetrahydropyrantriol crystallization mother liquor was vacuum concentrated. The hydroxypropyl tetrahydropyrantriol content in the mother liquor was 59%. The mother liquor was concentrated to dryness at 60°C and -0.099 MPa to obtain 361.3 g of a caramel-colored viscous substance. (2) Add 265 ml of ethanol to the concentrate, stir to completely dissolve the product, filter to remove impurities insoluble in ethanol, add 0 ml of purified water to the filtrate, and mix well; (3) Add 12.4 g of activated carbon, stir and heat to 45°C, decolorize for 1 hour, and filter to obtain a decolorized solution; (4) Stir and heat the decolorizing solution to 45°C, and start to add 133 ml of ether solvent for crystallization. After adding for 3 hours, keep the temperature at room temperature for 2 hours, then cool it down to 35°C at a rate of 5°C / h, continue to add 265 ml of ether solvent, and after adding for 3 hours, control the cooling rate to 4°C / h to reduce to 6°C, and keep the temperature at room temperature for 3 hours; (5) Filter, add 30 ml of ether to the filter cake to wash and remove impurities, collect the crystals, and dry them in vacuum at 45°C.

[0028] After testing, the crude product content of hydroxypropyl tetrahydropyrantriol was 84.4% and the yield was 67.9%.

[0029] Example 7 The difference from Example 1 is that the content of hydroxypropyl tetrahydropyrantriol in the mother liquor is 44%, and the other steps are the same as those in Example 1.

[0030] The obtained crude hydroxypropyl tetrahydropyrantriol was detected by HPLC, with a content of 70.9% and a yield of 61.2%.

[0031] Example 8 The difference from Example 2 is that the content of hydroxypropyl tetrahydropyrantriol in the mother liquor is 64%, and the other steps are the same as those in Example 2.

[0032] The obtained crude hydroxypropyl tetrahydropyrantriol was tested by HPLC, with a content of 90.3% and a yield of 71.4%.

[0033] In the present application, the HPLC graphs of the samples taken in Examples 1-8 show that all samples are of S configuration. From the graph, no two peaks are shown, so it is determined that all the above samples are solids of a single configuration.

[0034] In addition, since the mother liquor in the process of producing hydroxypropyl tetrahydropyrantriol by enzymatic method is used as raw material in this application, and carbonyl reductase has certain spatial structural selectivity, which is for products with a single (β, S) configuration, it is further determined that the obtained product is a product with a single (β, S) configuration. According to existing literature reports, the biological activity of the product with a single spatial configuration (β, S) is higher than that of the mixed configuration of (β, S) and (β, R), so the biological activity of the product of this application is also higher than that of the mixed product.

Claims

1. A process for recovering hydroxypropyl tetrahydropyrantriol from a mother liquor, characterized in that: The following steps are involved: (1) vacuum concentrating the mother liquor to dryness to obtain a concentrate; the mother liquor refers to the hydroxypropyl tetrahydropyrantriol crystallization mother liquor produced in the process of synthesizing hydroxypropyl tetrahydropyrantriol by enzymatic method; (2) adding an organic solvent I to the concentrate to completely dissolve the concentrate, filtering, removing insoluble matter, and obtaining a filtrate I, and adding or not adding purified water to the filtrate I; (3) Adding activated carbon, heating, decolorizing, filtering, and obtaining filtrate II; (4) adding organic solvent II to the filtrate II, growing crystals, and cooling; adding organic solvent II a second time, cooling, and growing crystals again; (5) Filter the material after crystallization in (4), wash the filter cake obtained after filtration, and dry it to obtain a crude product of hydroxypropyltetrahydropyrantriol.

2. The process for recovering hydroxypropyl tetrahydropyrantriol from a mother liquor according to claim 1, wherein: (1) During concentration, the temperature is 30℃~60℃, the vacuum degree is -0.1~-0.09 Mpa, and the concentration is performed until no condensate is distilled out.

3. The process for recovering hydroxypropyl tetrahydropyrantriol from a mother liquor according to claim 1, wherein: (2) The organic solvent I is selected from at least one of methanol, ethanol, acetonitrile or isopropanol; The volume mass ratio of the amount of organic solvent I added to the hydroxypropyl tetrahydropyrantriol contained in the mother liquor is (0.9-1.5) mL:1 g, and after dissolution, filtering is performed to remove impurities insoluble in the organic solvent I; The amount of purified water used is 0-5% of the volume of organic solvent I.

4. The process for recovering hydroxypropyl tetrahydropyrantriol from a mother liquor according to claim 1, wherein: In (3), the mass volume ratio of activated carbon added to filtrate I is (1~4) g:100 mL, and heating is carried out at 35℃~50℃.

5. The process for recovering hydroxypropyl tetrahydropyrantriol from a mother liquor according to claim 1, wherein: In step (4), the organic solvent II is selected from any one or more of ethyl acetate, acetone, butyl acetate, diethyl ether, and methyl tert-butyl ether.

6. The process for recovering hydroxypropyl tetrahydropyrantriol from a mother liquor according to claim 1, characterized in that: (4) The organic solvent II is added in a stepwise manner: Add organic solvent II to the filtrate at 30-50°C in one go, and complete the addition within 1-3 hours. After growing the crystal for 1.5-3 hours, cool it down at a rate of 4-6°C / h. Then, add organic solvent II for a second time at 20-40°C, and complete the addition in 2-3 hours. Then, cool the temperature down to 4-10°C at a rate of 2-6°C / h, and grow the crystal for 1-3 hours. The volume ratio of the organic solvent II added once to the organic solvent I is 0.5~1:1, and the volume ratio of the organic solvent II added twice to the organic solvent I is 1~2:

1.

7. The process for recovering hydroxypropyl tetrahydropyrantriol from a mother liquor according to claim 1, wherein: In (5), a detergent is used for washing, and the detergent is any one or more of the organic solvents II.

8. The process for recovering hydroxypropyl tetrahydropyrantriol from a mother liquor according to claim 1, comprising the steps of: (1) Using the hydroxypropyl tetrahydropyrantriol crystallization mother liquor produced in the process of synthesizing hydroxypropyl tetrahydropyrantriol by an enzymatic method as a raw material, concentrating at 30° C. to 60° C. and a vacuum degree of -0.1 to -0.09 MPa until no condensate is distilled out to obtain a concentrate; (2) adding an organic solvent I to the concentrate to completely dissolve the concentrate, filtering, removing insoluble matter, and obtaining a filtrate I, and adding or not adding purified water to the filtrate I; The organic solvent I is selected from at least one of methanol, ethanol, acetonitrile or isopropanol; the volume mass ratio of the organic solvent I added to the hydroxypropyl tetrahydropyrantriol contained in the mother liquor is (0.9-1.5) mL:1 g, and after dissolution, the impurities insoluble in the organic solvent I are removed by filtering; The amount of purified water used is 0-5% of the volume of organic solvent I; (3) Add activated carbon, heat to 35°C to 50°C, decolorize, and filter to obtain filtrate II; The mass volume ratio of activated carbon added to filtrate I is (1~4) g:100 mL; (4) Adding organic solvent II to the filtrate at 30-50°C in one go, and completing the addition within 1-3 hours. After growing the crystals for 1.5-3 hours, cool the mixture at a rate of 4-6°C / h. Then, the organic solvent II is added twice at 20-40°C for 2-3 hours, and the temperature is lowered to 4-10°C at a rate of 2-6°C / h, and the crystal is grown for 1-3 hours; The organic solvent II is selected from any one or more of ethyl acetate, acetone, butyl acetate, ethyl ether, and methyl tert-butyl ether; The volume ratio of the organic solvent II added once to the organic solvent I is 0.5-1:1, and the volume ratio of the organic solvent II added twice to the organic solvent I is 1-2:1; (5) growing crystals, filtering, washing the resulting filter cake with an organic solvent II, and drying to obtain a crude product of hydroxypropyltetrahydropyrantriol.

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