A method for the synthesis of epihalohydrin

Abstract

The application belongs to the technical field of sugar synthesis chemistry, and particularly relates to a synthesis method of eplactinose. The method of the application uses beta-octanoyl lactose as a raw material, and eplactinose is obtained by modifying and inverting 2-OH of a glucose fragment. The raw material is easy to obtain, the method is simple in process and low in cost, and is suitable for large-scale production.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of sugar synthesis chemistry, and particularly relates to a method for synthesizing epilactose. BACKGROUND

[0002] The information disclosed in this background section is intended to provide an overview of the general background of the application and is not necessarily a complete description of the background of the application. The information disclosed in this background section is not necessarily admitted to be prior art by virtue of its inclusion in this section.

[0003] Epilactose (I), also known as epilactose, has a chemical structure of galactose-β-(1→4)-mannose, and is an isomer of lactose (II). Epilactose is a rare reducing disaccharide, and has important biological functions and beneficial activities, such as promoting the absorption of minerals in the intestinal tract and reducing the effects of arteriosclerosis.

[0004]

[0005] Due to the important application value of epilactose, its preparation method has been paid great attention. The previous chemical synthesis method (Wang Jiayao, Jiang Rui, Liang Xiaomei, Jin Shuhui, Wang Daoquan, Zhang Jianjun. Efficient Synthesis of Epilactose[J]. Chin. J. Org. Chem., 2017, 37(2): 375-384.; Huang S, Yu H, Chen X. Disaccharides as Sialic Acid Aldolase Substrates: Synthesis of Disaccharides Containing a Sialic Acid at the Reducing End [J]. Angewandte Chemie International Edition, 2007, 46(13):2249-2253 DOI:10.1002 / anie.200604799.) adopts the method of coupling galactose and mannose fragments, which has long general route, complicated process and low yield. And the existing enzyme method for synthesizing epilactose (Ito, S., Taguchi, H., Hamada, S. et al. Enzymatic properties of cellobiose 2-epimerase from Ruminococcus albus and the synthesis of rare oligosaccharides by the enzyme. Appl Microbiol Biotechnol 79, 433-441 (2008). https: / / doi.org / 10.1007 / s00253-008-1449-7) has poor reproducibility, difficult separation and purification, and is difficult to prepare in large quantities. SUMMARY

[0006] In view of the problems in the prior art, the present application provides a synthesis method of epilactose, which is easy to obtain raw materials and suitable for scale-up production.

[0007] To achieve the above object, the present application adopts the following technical scheme.

[0008] A synthesis method of epilactose, comprising the following steps:

[0009] (1) beta-octacetyl lactose is mixed with PCIs in an organic solvent, and the mixture is reacted at room temperature. After the reaction is completed, the mixture is cooled, and the intermediate 1 is separated.

[0010] (2) The intermediate 1, N,N-dimethylformamide (DMF) and water are reacted in an organic solvent at room temperature. After the reaction is completed, the intermediate 2 is separated.

[0011] (3) The intermediate 2 and acetic anhydride are reacted in an organic solvent. After the reaction is completed, the intermediate 3 is separated.

[0012] (4) The intermediate 3 and sodium borohydride are reacted in an organic solvent. After the reaction is completed, the intermediate 4 is separated.

[0013] (5) The intermediate 4 and sodium methoxide are reacted in methanol at room temperature. After the reaction is completed, the product is separated and purified.

[0014] In step (1), the molar ratio of beta-octacetyl lactose to PCIs is 1:(1-2.5); preferably 1:(1.5-2.5); more preferably 1:(2-2.5).

[0015] In step (1), the temperature for mixing and cooling is -10°C to 0°C; preferably -10°C to -5°C.

[0016] In step (1), the separation step is to add a saturated sodium bicarbonate solution with a temperature not higher than 0°C to the reaction system until the pH is greater than 7, to separate the organic phase, and to remove the solvent.

[0017] In step (2), the mass ratio of water to beta-octacetyl lactose is 2:5. The volume ratio of DMF to water is 1:4; the volume ratio of DMF to organic solvent is 1:100.

[0018] In step (2), the separation step is to add an equal amount of dichloromethane to the reaction system after removing the solvent to the original volume, to wash with saturated brine, to separate the organic phase, and to remove the solvent.

[0019] In step (3), the molar ratio of acetic anhydride to beta-octacetyl lactose is (5-10):1; preferably (5-7.5):1.

[0020] In step (3), the separation step is to dilute the reaction system with 4-5 times the volume of dichloromethane, then adjust the pH to greater than 7 with a saturated sodium bicarbonate solution, separate the organic phase, and remove the solvent.

[0021] In step (4), the molar ratio of sodium borohydride to beta-octacetyl lactose is (1-5):1; preferably (3-5):1.

[0022] In step (4), the separation step is to pour the reaction system into 1N hydrochloric acid solution at 0-4℃, then extract with dichloromethane, and the extraction is performed 1-3 times; the dichloromethane phase obtained by separation is dried, and the solvent is removed; the ratio of hydrochloric acid solution to beta-octaacetyl lactose is 2 mL:1 g, and the ratio of dichloromethane to beta-octaacetyl lactose is 5 mL:1 g.

[0023] In step (5), the molar ratio of beta-octaacetyl lactose to sodium methoxide is (10-20):1.

[0024] In step (5), the separation and purification step is to remove the solvent after neutralization of the reaction system, and then add methanol and methyl tert-butyl ether in a volume ratio of 1:2; filter and dry to obtain the product; the added volume of methanol and methyl tert-butyl ether is 0.5-1 times of the reaction system.

[0025] In the above steps, the concentration of beta-octaacetyl lactose and each intermediate in the organic solvent is not higher than 0.5 mol / L; preferably 0.05-0.5 mol / L; more preferably 0.05-0.15 mol / L. The organic solvent is selected from at least one of dichloromethane, acetone, methanol and dimethyl sulfoxide (DMSO).

[0026] The present application has the following advantages:

[0027] The present application uses commercially available beta-octaacetyl lactose as a starting material, and through 5-step continuous conversion, efficiently modifies and inverts the 2-OH of the glucose fragment to obtain the eptolactose product, overcoming the difficulties in preparing eptolactose by traditional methods, and promoting the development and application of eptolactose functions. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 is eptolactose 1 HNMR spectrum;

[0029] Figure 2 is eptolactose 13 C NMR spectrum;

[0030] Figure 3 is the high-resolution mass spectrum (HRMS) of eptolactose;

[0031] Figure 4 is the HPLC chart of eptolactose. DETAILED DESCRIPTION

[0032] All materials used in the experiments of the present application are commercially available products unless otherwise specified. Unless otherwise specified, room temperature refers to 10-30℃; low temperature refers to not higher than 5℃, especially -10-5℃; ice water is 0-4℃; and the pH of weak base is 7.1-8.5.

[0033] A preparation method of eptolactose, the reaction route is as follows:

[0034] .

[0035] Specifically, the above preparation method comprises the following steps:

[0036] (1) beta-octanoyllactose and PCl5 are mixed in dichloromethane at a molar ratio of 1: (1-2.5) at -10°C-0°C, and the reaction is carried out at room temperature. After monitoring the disappearance of the raw material, the reaction is stopped, the reaction system is cooled to -10°C-0°C, and the intermediate 1 is separated and directly connected to the next step.

[0037] Specifically, the separation step is: saturated sodium bicarbonate ice water solution is added to the reaction system to be weakly alkaline (pH>7), and the organic phase is separated by standing. The solvent is removed by reduced pressure evaporation to obtain oily intermediate 1.

[0038] (2) Intermediate 1 is dissolved in acetone, and 1:4 volume ratio of DMF and water is added. The volume ratio of DMF and acetone is 1:100, and the reaction is carried out at room temperature. After monitoring the disappearance of the raw material, the intermediate 2 is separated and directly connected to the next step.

[0039] Specifically, the separation step is: the solvent is removed by reduced pressure removal to obtain an oily substance, which is then dissolved in an equal volume of dichloromethane, washed with saturated brine, and the organic phase is separated by standing. The organic phase is washed once more, and the solvent is removed by reduced pressure evaporation to obtain oily intermediate 2.

[0040] (3) Intermediate 2 and acetic anhydride are reacted in DMSO, and the molar amount of acetic anhydride added is 5-10 times that of beta-octanoyllactose. After monitoring the disappearance of the raw material, the intermediate 3 is separated and directly connected to the next step.

[0041] Specifically, the separation step is: the reaction system is diluted with 4-5 times the volume of dichloromethane, and then the pH is adjusted to greater than 7 with saturated sodium bicarbonate solution. The organic phase is separated by standing, and the solvent is removed.

[0042] (4) Intermediate 3 and sodium borohydride are reacted in methanol, and the molar amount of sodium borohydride added is 1-5 times that of beta-octanoyllactose. After monitoring the disappearance of the raw material, the intermediate 4 is separated and directly connected to the next step.

[0043] Specifically, the separation step is: pour the reaction system into a 0°C-4°C, 1N hydrochloric acid solution, then extract with dichloromethane, dry the dichloromethane phase obtained, and remove the solvent; wherein the ratio of hydrochloric acid solution to beta-octanoyllactose is 2mL:1g, and the ratio of dichloromethane to beta-octanoyllactose is 5mL:1g.

[0044] (5) intermediate 4 and sodium methoxide in methanol at room temperature, the amount of sodium methoxide added is 1: (10~20) of the molar amount of beta-octacetyl lactose; after monitoring the end of the reaction, the product isobutyl lactose is obtained by separation and purification;

[0045] Specifically, the separation and purification step is: the reaction system is neutralized to neutral by adding an acidic resin, the acidic resin is removed by filtration, then concentrated under reduced pressure until no fraction is obtained, then 0.5~1 times the volume of methanol and methyl tert-butyl ether in a volume ratio of 1:2 is added to the residue, stirred, cooled to 0°C, and then filtered after continued stirring; the filtrate is dried to obtain a white powder product.

[0046] In the above steps, the concentration of beta-octacetyl lactose and each intermediate in the organic solvent is not higher than 0.5 mol / L.

[0047] The application will be further described in conjunction with the examples and drawings, but the application is not limited by the following examples. Unless otherwise specified, room temperature refers to 10°C~30°C; low temperature refers to not higher than 5°C, especially -10°C~5°C; ice water is 0°C~4°C; weakly basic pH is 7.1~8.5.

[0048] Example 1 Synthesis of isobutyl lactose

[0049] (1) 10.0 g (14.7 mmol) of beta-octacetyl lactose is added to 100 ml of dichloromethane under stirring, the system is stirred and cooled to below -5°C, then 6.76 g (32.5 mmol) of PCl5 is added in batches, the system temperature is controlled below -5°C during the addition; after the addition is completed, the system temperature is raised to 25°C, then the stirring is continued for 6 hours; after the TLC detection of the disappearance of the raw material, the system is cooled to below -5°C, then slowly poured into a vigorously stirred saturated sodium bicarbonate ice water solution, stirred for 30 minutes, the system is detected to be weakly alkaline, then separated into an organic phase by standing; the obtained oil-like intermediate 1 is directly used in the next step after being concentrated under reduced pressure.

[0050] (2) Intermediate 1 is dissolved in 100 ml of acetone at room temperature, 4 ml of water and 1 ml of DMF are added to the system, then stirred and reacted at room temperature, about 6 hours after the TLC detection of the disappearance of the raw material, the system is concentrated under reduced pressure, the obtained oil-like material is dissolved in 100 ml of dichloromethane, washed with saturated brine twice, then the organic phase is separated, concentrated under reduced pressure to obtain oil-like intermediate 2 which is directly used in the next step.

[0051] (3) Intermediate 2 was dissolved in 10 mL of DMSO and 10 mL of acetic anhydride, and the reaction was stirred at room temperature until the starting material disappeared according to TLC detection. Then the system was diluted with 100 mL of dichloromethane and poured into a saturated aqueous sodium bicarbonate solution and stirred until it became weakly alkaline. The dichloromethane phase was separated and concentrated under reduced pressure to obtain oily intermediate 3, which was used directly in the next step.

[0052] (4) Intermediate 3 was dissolved in 100 mL of methanol, and the temperature was lowered to below -5°C while stirring. Then 2.23 g (58.9 mmol) of sodium borohydride powder was added portionwise, and the reaction was stirred at -5°C for 30 minutes and then at room temperature for about 6 hours. The starting material disappeared according to TLC detection. The system was poured into 20 mL of 1 N hydrochloric acid ice water solution, and stirred for 30 minutes. The aqueous phase was extracted with 50 mL of dichloromethane three times. The dichloromethane phases were combined and concentrated under reduced pressure to obtain oily intermediate 4, which was used directly in the next step.

[0053] (5) Intermediate 4 was dissolved in 50 mL of methanol, and 50 mg (0.92 mmol) of sodium methoxide was added. The reaction was stirred at room temperature for 1 hour until there was no starting material and intermediate according to HPLC detection. The system was neutralized to neutral with an acidic resin. After the acidic resin was removed by filtration, the system was concentrated under reduced pressure until there was no fraction, and then 10 mL of methanol and 20 mL of methyl tert-butyl ether were added to the concentrated residue and stirred for 1 hour. Then the system was cooled to 0°C and continued to stir for 1 hour, and then filtered. The filter was dried by hot air to obtain 1.76 g of white powder product, with a total yield of 35% and a purity of 100% (HPLC method).

[0054] The above product was analyzed by 1 H NMR, 13 C NMR and HRMS spectra, respectively, as shown in Figures 1-3 :

[0055] 1 H NMR (400 MHz, D2O) δ: 5.21 (d, 0.61 H, J = 1.6 Hz), 4.95 (s, 0.39H), 4.45-4.50 (dd, 1H, J1 = 7.6 Hz, J2 = 2.4Hz), 3.99-4.05 (m, 1.37H), 3.93-3.98 (m, 2H), 3.74-3.87 (m, 3H), 3.67-3.73 (m, 1H), 3.53-3.62 (m, 1.33 H).

[0056] 13C NMR (100 MHz, D2O) δ: 103.14, 93.88, 76.66, 75.46, 72.60, 71.12, 71.05, 70.27, 70.21, 69.11, 68.69, 61.20, 60.43; (93.72, 76.25, 75.04, 71.90, 70.72 are peaks of isomers).

[0057] Hydrogen spectrum, carbon spectrum data and literature are consistent (Disaccharides as Sialic Acid Aldolase Substrates: Synthesis of Disaccharides Containing a Sialic Acid at the Reducing End [J]. Angewandte Chemie International Edition, 2007, 46(13): 2249-2253; Efficient Synthesis of Epilactose [J]. Chin. J. Org. Chem. , 2017, 37(2): 375-384.).

[0058] HRMS (ESI, m / z) calculated for C 12 H 22 O 11 Cl [M+H] + : 377.0851, found 377.0856; molecular formula is C 12 H 22 O 11 .

[0059] The above eptolactose sample was prepared into a 50 mg / mL solution with acetonitrile / water (80:20 by volume) as the solvent for HPLC detection. The chromatographic conditions are as follows:

[0060] Chromatographic column: Durashell NH2, φ4.6x250mmx5μm;

[0061] Column temperature: 40℃;

[0062] Mobile phase: acetonitrile / water = 80:20;

[0063] Flow rate: 1.0 mL / min;

[0064] Detector: Evaporative Light Scattering Detector (ELSD).

[0065] The HPLC chart of eptolactose sample is as follows:Figure 4 The peak time is about 14.83 min, and the content is 100% according to the area normalization method.

[0066] Example 2 Synthesis of Epihalactose

[0067] (1) 100.0 g of beta-octacetyl lactose was added to 1 liter of dichloromethane under stirring, and the system was cooled to below -5°C, then 67.6 g of PCl5 was added in batches, and the temperature of the system was controlled below -5°C during the addition. After the addition was completed, the temperature of the system was raised to 25°C, and then the stirring reaction was continued for 6 hours. After the raw material was detected to be consumed by TLC, the system was cooled to below -5°C, then slowly poured into a vigorously stirred saturated sodium bicarbonate ice water solution, stirred for 30 minutes, and the system was detected to be weakly alkaline, then the organic phase was separated by standing. The obtained oily intermediate 1 was directly used in the next step.

[0068] (2) Intermediate 1 was dissolved in 1 liter of acetone at room temperature, 40 ml of water and 10 ml of DMF were added to the system, then the system was stirred and reacted at room temperature for about 6 hours, then the system was concentrated under reduced pressure after TLC detection of the raw material consumption, the obtained oily substance was dissolved in 1 liter of dichloromethane, washed twice with saturated brine, then the organic phase was separated, and concentrated under reduced pressure to obtain oily intermediate 2, which was directly used in the next step.

[0069] (3) Intermediate 2 was dissolved in 100 ml of DMSO and 100 ml of acetic anhydride, and the system was stirred and reacted at room temperature until the raw material was detected to be consumed by TLC, then the system was diluted with 1 liter of dichloromethane, poured into a saturated sodium bicarbonate aqueous solution, and stirred to neutralize to weak alkaline. The dichloromethane phase was separated by standing, and concentrated under reduced pressure to obtain oily intermediate 3, which was directly used in the next step.

[0070] (4) Intermediate 3 was dissolved in 1 liter of methanol, and the system was cooled to below -5°C under stirring, then 22.3 g of sodium borohydride powder was added in batches, and the system was stirred and reacted at -5°C for 30 minutes, then reacted at room temperature until the raw material was detected to be consumed by TLC. The system was poured into 200 ml of 1N hydrochloric acid ice water solution, stirred for 30 minutes, then the water phase was extracted with dichloromethane for 3 times, each time using 500 ml of dichloromethane, the three dichloromethane phases were combined, and concentrated under reduced pressure to obtain oily intermediate 4, which was directly used in the next step.

[0071] (5) Intermediate 4 was dissolved in 500 ml of methanol, 0.5 g of sodium methoxide was added, and the system was stirred and reacted at room temperature for 1 hour, then HPLC detection was performed until there was no raw material and intermediate, and the system was neutralized to neutral by adding an acidic resin. After the acidic resin was removed by filtration, the system was concentrated under reduced pressure until there was no distillate, then 100 ml of methanol and 200 ml of methyl tert-butyl ether were added to the concentrated residue, stirred for 1 hour, and white powder was generated. The system was cooled to 0°C and continued to stir for 1 hour, then the white powder product was obtained by filtration, and dried by hot air to obtain 18.6 g of product, with a total yield of 37% and a purity of 100% (HPLC method).

[0072] Example 3 Synthesis of Epi-lactose

[0073] (1) Under stirring, 1 kg of beta-octacetyl lactose was added into 10 L of dichloromethane, the system was stirred and cooled to about -10°C, then 600 g of PCl5 was added in batches, the temperature of the system was controlled below -5°C during the addition. After the addition was completed, the temperature of the system was raised to 25°C, then the stirring was continued for 6 hours. After the raw material was detected to disappear by TLC, the system was cooled to below -5°C, then slowly poured into a vigorously stirred saturated sodium bicarbonate ice water solution, stirred until the system was weakly alkaline (pH = 7.5), then separated the organic phase by standing. The organic phase was concentrated under reduced pressure to obtain an oily intermediate 1 which was directly used in the next step.

[0074] (2) The intermediate 1 was dissolved in 10 L of acetone at room temperature, 400 mL of water and 100 mL of DMF were added into the system, then the stirring reaction was continued at room temperature until the raw material was detected to disappear by TLC. The system was concentrated under reduced pressure, the obtained oily substance was dissolved in 10 L of dichloromethane, then washed twice with equal volume of saturated brine to separate the organic phase, and concentrated under reduced pressure to obtain an oily intermediate 2 which was directly used in the next step.

[0075] (3) The intermediate 2 was dissolved in 1 L of DMSO and 1 L of acetic anhydride, the stirring reaction was continued at room temperature until the raw material was detected to disappear by TLC, then the system was diluted with 10 L of dichloromethane, poured into a saturated sodium bicarbonate aqueous solution and stirred to neutralize to weak alkaline (pH = 7.5). The dichloromethane phase was separated by standing, and concentrated under reduced pressure to obtain an oily intermediate 3 which was directly used in the next step.

[0076] (4) The intermediate 3 was dissolved in 10 L of methanol, stirred and cooled to about -5°C, then 200 g of sodium borohydride powder was added in batches, stirred at -5°C for 30 minutes, then reacted at room temperature until the raw material was detected to disappear by TLC. The system was poured into 2 L of 1 N hydrochloric acid ice water solution, stirred for 30 minutes, then the water phase was extracted with dichloromethane for 3 times, 5 L of dichloromethane was used each time. The dichloromethane phases were combined and concentrated under reduced pressure to obtain an oily intermediate 4 which was directly used in the next step.

[0077] (5) The intermediate 4 was dissolved in 5 L of methanol, 5 g of sodium methoxide was added, stirred at room temperature for 1 hour, then HPLC detection was performed until there was no raw material and intermediate. Acidic resin was added to neutralize the system to neutral. After the acidic resin was removed by filtration, the system was concentrated under reduced pressure until there was no distillate, then 1 L of methanol and 2 L of methyl tert-butyl ether were added into the concentrated residue, stirred for 1 hour, then the system was cooled to 0°C and continued to stir until there was a large amount of insoluble substance. The insoluble substance was filtered and dried to obtain 191 g of white powder product, the total yield was 38%, and the purity was 100% (HPLC method).

Claims

1. A method for synthesizing ipilactose, characterized in that, Includes the following steps: (1) beta-octaacetyllactose and PCl5 were mixed in an organic solvent and reacted at room temperature. After the reaction was completed, the temperature was lowered and intermediate 1 was obtained by separation. ; (2) Intermediate 1 reacts with DMF and water in an organic solvent at room temperature. After the reaction is complete, intermediate 2 is obtained by separation: ; (3) Intermediate 2 and acetic anhydride react in an organic solvent, and intermediate 3 is obtained after the reaction is complete: ; (4) Intermediate 3 and sodium borohydride react in an organic solvent, and intermediate 4 is obtained after the reaction is complete: ; (5) Intermediate 4 and sodium methoxide react in methanol at room temperature. After the reaction is complete, the product is separated and purified. In step (2), the mass ratio of water to beta-octaacetyl lactose in step (1) is 2:5; the volume ratio of DMF to water is 1:4; and the volume ratio of DMF to organic solvent is 1:

100. In step (2), the organic solvent is acetone.

2. The synthesis method according to claim 1, characterized in that, In step (1), the molar ratio of beta-octaacetyl lactose to PCl5 is 1:(1~2.5); In step (3), the molar ratio of acetic anhydride to beta-octaacetyl lactose in step (1) is (5~10):1; In step (4), the molar ratio of sodium borohydride to beta-octaacetyl lactose in step (1) is (1~5):1; In step (5), the molar ratio of sodium methoxide to beta-octaacetyl lactose in step (1) is 1:(10~20); The concentration of beta-octaacetyl lactose and its intermediates in organic solvents shall not exceed 0.5 mol / L; In step (1), the mixing and cooling temperatures are -10℃ to 0℃; In step (1), the organic solvent is dichloromethane; in step (3), the organic solvent is DMSO; in step (4), the organic solvent is methanol.

3. The synthesis method according to claim 1, characterized in that, In step (1), the molar ratio of beta-octaacetyl lactose to PCl5 is 1:(1.5~2.5); In step (3), the molar ratio of acetic anhydride to beta-octaacetyl lactose in step (1) is (5~7.5):1; In step (4), the molar ratio of sodium borohydride to beta-octaacetyl lactose in step (1) is (3~5):1; The concentration of beta-octaacetyl lactose and its intermediates in organic solvents is 0.05 mol / L to 0.5 mol / L; In step (1), the mixing and cooling temperatures are -10℃ to -5℃.

4. The synthesis method according to claim 1, characterized in that, In step (1), the molar ratio of beta-octaacetyl lactose to PCl5 is 1:(2~2.5); The concentrations of beta-octaacetyl lactose and its intermediates in organic solvents range from 0.05 mol / L to 0.15 mol / L.

5. The synthesis method according to claim 1, characterized in that, In step (1), the separation step is to add a saturated sodium bicarbonate solution at a temperature not higher than 0°C to the reaction system until the pH is greater than 7, let it stand to separate the organic phase, and remove the solvent; In step (2), the separation step is to remove the solvent from the reaction system, add an equal amount of dichloromethane to the original volume, wash with saturated brine, let stand to separate the organic phase, and remove the solvent; In step (3), the separation step involves adding 4 to 5 times the volume of dichloromethane to dilute the reaction system, then adjusting the pH to be greater than 7 with saturated sodium bicarbonate solution, allowing it to stand to separate the organic phase, and removing the solvent. In step (4), the separation step is to pour the reaction system into a 1N hydrochloric acid solution at 0℃~4℃, and then extract it with dichloromethane. The extraction is repeated 1-3 times. The dichloromethane phase obtained by separation is dried to remove the solvent. The ratio of hydrochloric acid solution to beta-octaacetyl lactose in step (1) is 2mL:1g, and the ratio of dichloromethane to beta-octaacetyl lactose in step (1) is 5mL:1g. In step (5), the separation and purification steps are as follows: after neutralizing the system, the solvent is removed, and methanol and methyl ether with a volume ratio of 1:2 are added to the residue. The mixture is then filtered and dried to obtain the product. The volume of methanol and methyl ether added is 0.5 to 1 times that of the reaction system.

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