Preparation method of tetrahydronaphthalene [1, 2-b] furan-2 (3H)-ketone compound

Abstract

The invention discloses a preparation method of a tetrahydronaphthalene [1, 2-b] furan-2 (3H)-ketone compound, and belongs to the technical field of organic synthesis. Comprising the following steps: reacting a compound 1 with tetra-n-butylammonium fluoride to obtain a compound 2; reacting the compound 2, alkali and L-DTTA to obtain a compound 3; reacting the compound 3 with methanesulfonic acid to obtain a crude product of the tetrahydronaphthalene [1, 2-b] furan-2 (3H)-ketone compound; and purifying the crude product of the tetrahydronaphthalene [1, 2-b] furan-2 (3H)-ketone compound to obtain the tetrahydronaphthalene [1, 2-b] furan-2 (3H)-ketone compound. The product obtained by the preparation method has the advantages of high yield and purity, low isomer content and low production cost.

Description

Technical Field

[0001] This invention provides a method for preparing a tetrahydronaphtho[1,2-b]furan-2(3H)-one compound, belonging to the field of organic synthesis technology. Background Technology

[0002] Tetrahydronaphtho[1,2-b]furan-2(3H)-one compound, structural formula: Its Chinese chemical name is (3S,3aS,9bR)-8-(2-bromobenzyl)oxy)-3-((dimethyl)aminomethyl-6,9-dimethyl-3a,4,5,9b-tetrahydronaphtho[1,2-b]furan-2(3H)-one mesylate, and its English chemical name is (3S,3aS,9bR)-8-((2-bromobenzyl)oxy)-3-((dimethylamino)methyl)-6,9-dimethyl-3a,4,5,9b-tetrahydronaphtho[1,2-b]furan-2(3H)-one mesylate. It is an effective drug for the treatment of rheumatoid arthritis.

[0003] In Chinese patent CN111247132B, the preparation method is as follows: Compound 51 (i.e., compound 2 of the present invention) is prepared using the method of Example 1 of the patent, and compound 59 (i.e., compound 4 of the present invention) is prepared using the method of Example 4 of the patent: Compound (3aS,9bR)-8-(2-bromobenzyloxy)-6,9-dimethyl-3-methylene-3a,4,5,9b-tetrahydronaphtho[1,2-b]furan-2(3H)-one (compound 51) (1.0 g, 2.43 mmol, 1.0 eq) and dimethylamine hydrochloride (0.3 g, 3.64 mmol, 1.5 eq) are dissolved in 20 ml of ethanol, and triethylamine (0.37 g, 3.64 mmol, 0.51 ml, 1.5 eq) is added dropwise at 0°C. 0.5 eq), naturally heated to room temperature and stirred, monitored by TLC. After compound 51 was completely consumed, ethanol was removed by low-temperature vacuum distillation, followed by extraction with dichloromethane and water. The organic layer was washed with saturated brine, dried over anhydrous Na2SO4, and subjected to column chromatography (PE / EA = 20:1-EA) to obtain a white solid, which is compound (3R / S,3aS,9bR)-8-(2-bromobenzyloxy)-3-dimethylaminomethyl-6,9-dimethyl-3a,4,5,9b-tetrahydronaphtho[1,2-b]furan-2(3H)-one (1.1 g, 99%).

[0004] This preparation method produces high purity, but requires two column chromatography steps, which is not conducive to large-scale production. Furthermore, the product obtained by this method has a high content of isomers.

[0005] For chiral isomers, chiral column methods are commonly used for separation, such as those described in "Chromatic Chiral Separation Technology and Application" (Yuan Liming et al., 2020, Chemical Industry Press): chiral mobile phase additive method, chiral derivatization reagent method, chiral gas chromatography, etc. However, this method is expensive and not suitable for large-scale production.

[0006] For chiral isomers, since their molecular structures are mirror images of each other but cannot be superimposed, conventional achiral separation techniques are difficult to achieve effective separation. Therefore, chiral column-related techniques and supporting methods are commonly used in the industry for precise separation and purification. Among them, "Chromatographic Chiral Separation Technology and Application" (Yuan Liming et al., 2020, Chemical Industry Press) describes chiral mobile phase additive methods, chiral derivatization reagent methods, and chiral gas chromatography methods.

[0007] However, this type of separation method based on chiral columns has significant limitations: the preparation process of chiral stationary phase materials is complex and costly, and their service life is limited, with frequent replacements significantly increasing the cost of production consumables; at the same time, special solvents or auxiliaries are often required in chiral separation processes, and subsequent solvent recovery and treatment are difficult and environmental costs are high; in addition, the separation efficiency of chromatography is affected by various parameters such as flow rate and temperature, and problems such as unstable separation effect and limited production capacity are prone to occur during large-scale production. Therefore, overall, it is not suitable for industrial-scale production scenarios.

[0008] Patent WO2021143853A1 discloses a tetrahydronaphtho[1,2-b]furan-2(3H)-one compound and its crystal form study, and its reaction route is as follows:

[0009] .

[0010] The patent describes a method that, after three recrystallizations following the reaction, yields compound VII with a yield of only 72%. Furthermore, VII contains 90% S-configuration and 10% R-configuration, requiring three more recrystallizations to obtain a compound with a single S-configuration. This patented preparation method generates numerous isomers during the process, increasing purification difficulty and reducing yield. Summary of the Invention

[0011] This invention provides a method for preparing tetrahydronaphtho[1,2-b]furan-2(3H)-one compounds. The preparation method yields products with high yield and purity, and has low isomer content and low production cost.

[0012] Terminology Explanation: Unless otherwise defined, all technical terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which the subject matter pertains. Unless otherwise stated, all patents, patent inventions, and publications cited throughout this document are incorporated herein by reference in their entirety. Where multiple definitions exist for terms, the definitions provided in this chapter shall prevail.

[0013] It should be understood that the above brief description and the following detailed description are exemplary and for illustrative purposes only, and do not limit the subject matter of the invention in any way. In this invention, the singular is used in conjunction with the plural unless otherwise specifically stated. It should also be noted that, unless otherwise stated, the use of “or” or “or” means “and / or”. Furthermore, the use of the term “comprising” and other forms such as “including,” “containing,” and “contains” are not limiting.

[0014] The definition of standard chemical terms can be found in the reference "Basic Organic Chemistry, Xing Qiyi, 2005 edition".

[0015] Unless otherwise specified, conventional methods within the scope of the art, such as HPLC, weighing determination, etc., shall be used.

[0016] Unless specifically defined herein, the use of all commercially available products herein employs standard techniques. For example, it may be carried out using the manufacturer's instructions for use with the kit, or in accordance with methods known in the art or the description of this invention. The techniques and methods described herein can generally be implemented according to conventional methods well known in the art, based on the descriptions in the various summary and more specific documents cited and discussed in this specification.

[0017] In a first aspect, the present invention provides a method for preparing a tetrahydronaphtho[1,2-b]furan-2(3H)-one compound, comprising the following steps: (1) Compound 1 was reacted with tetra-n-butylammonium fluoride to obtain compound 2; (2) Compound 2 reacts with a base and L-DTTA to give compound 3; (3) Compound 3 reacts with methanesulfonic acid to give crude tetrahydronaphtho[1,2-b]furan-2(3H)-one; (4) The crude product of tetrahydronaphtho[1,2-b]furan-2(3H)-one compound was purified to obtain tetrahydronaphtho[1,2-b]furan-2(3H)-one compound; Compound 1 is: Compound 2 is: Compound 3 is: The tetrahydronaphtho[1,2-b]furan-2(3H)-one compound is: .

[0018] Further, the molar ratio of compound 1 and tetra-n-butylammonium fluoride in step (1) is 1:(3-4.5).

[0019] Preferably, the molar ratio of compound 1 and tetra-n-butylammonium fluoride in step (1) is 1:3, 1:3.5, 1:4, 1:4.5 or any combination thereof.

[0020] Further, the reaction described in step (1) is as follows: compound 1 and tetra-n-butylammonium fluoride react at 20-30℃ for 2-4 hours.

[0021] Preferably, the reaction in step (1) further includes the addition of a polymerization inhibitor.

[0022] More preferably, the polymerization inhibitor includes resorcinol.

[0023] Furthermore, the base mentioned in step (2) is dimethylamine.

[0024] Furthermore, the solvent for the dimethylamine is tetrahydrofuran.

[0025] Preferably, the concentration of the dimethylamine is 2M.

[0026] Preferably, the amount of dimethylamine tetrahydrofuran solution added is compound 2: dimethylamine tetrahydrofuran solution = 1g: (0.1-1)mL.

[0027] Further, the molar ratio of compound 2 and L-DTTA in step (2) is 1:(1-1.5).

[0028] Preferably, the molar ratio of compound 2 and L-DTTA in step (2) is 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5 or any combination thereof.

[0029] Furthermore, the solvent for the reaction in step (2) is dichloromethane.

[0030] Further, the reaction described in step (2) is as follows: compound 2 is first reacted with a base at 20-30℃ for 10-20h, and then L-DTTA is added and reacted at 20-30℃ for 1-2h.

[0031] Further, the reaction described in step (3) is as follows: compound 3 is extracted with an inorganic base and the organic phase is collected. The organic phase is then reacted with methanesulfonic acid at 20-30℃ for 0.5-2h.

[0032] Furthermore, the inorganic base is at least one selected from sodium hydroxide, potassium carbonate, potassium hydroxide, and sodium carbonate.

[0033] Further, the purification described in step (4) is recrystallization.

[0034] Preferably, the recrystallization is performed by mixing the solvent and the crude tetrahydronaphtho[1,2-b]furan-2(3H)-one compound at 30-40°C and stirring for 2-3 hours. The mixture is then cooled to 10-20°C, filtered, the filter cake is washed with acetone, the filter cake is collected, and dried at 40-50°C for 2-3 hours.

[0035] Preferably, the solvent for recrystallization is acetone containing 1-5 wt% water.

[0036] Beneficial effects: This invention improves the purity and yield of compound 4 (tetrahydronaphtho[1,2-b]furan-2(3H)-one compound) and reduces the content of isomers by setting specific reaction steps (such as step 2), using specific reaction reagents (such as dimethylamine THF solution), specific reagent dosages, and specific purification methods. The specific reaction steps, reagents, and reagent dosages reduce the content of chiral isomers in the preparation process. Combined with the specific purification method of this invention, the chiral isomer content of the final product can be reduced without using chiral column purification, thus saving production costs. Attached Figure Description

[0037] Figure 1 The image shows the PXRD results of the tetrahydronaphtho[1,2-b]furan-2(3H)-one compound from Example 1. Detailed Implementation

[0038] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention.

[0039] Before further describing specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terminology used in the embodiments of the present invention is for describing specific embodiments and not for limiting the scope of protection of the present invention.

[0040] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the invention, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0041] The reaction route of this invention:

[0042] The tetrahydronaphtho[1,2-b]furan-2(3H)-one compound is compound 4.

[0043] Example 1: A method for preparing a tetrahydronaphtho[1,2-b]furan-2(3H)-one compound. The preparation method is as follows: Step 1: Preparation of Compound 2. Prepare a 100L reactor. Add THF (tetrahydrofuran) and Compound 1 (1.0 eq) to the reactor and stir. The ratio of Compound 1:THF is 1 g:50 mL. Add resorcinol (polymerization inhibitor, 0.1 eq) and adjust the temperature to 30°C. Dropwise add a THF solution of TBAF (tetra-n-butylammonium fluoride, 3.0 eq), maintaining the temperature at 30°C. TBAF solution preparation: Add 1 mL of THF to every 1 g of TBAF and stir until dissolved. After the addition is complete, stir at 30°C for 3 hours. HPLC analysis shows that Compound 1 is ≤1 wt%.

[0044] After the reaction was complete, the reaction solution was concentrated under reduced pressure at 45°C until no distillate was obtained. After concentration, the concentrate was extracted twice with ethyl acetate, THF, and purified water. The organic phase was collected, and resorcinol (0.1 eq) was added and stirred for 5 minutes. The organic phase was then concentrated under reduced pressure at 45°C until no distillate was obtained.

[0045] MTBE was added to the concentrate until dissolved, and the mixture was stirred and transferred to a 50L reactor. n-Heptane was added dropwise to the reactor, and stirring continued for 2 hours. The reaction mixture was filtered, and the filter cake was washed with a mixed solvent of MTBE and n-heptane. The mixed solvent was prepared as follows: MTBE and n-heptane were mixed in a 1:1 volume ratio. The filter cake was collected and dried at 50°C for 2 hours to obtain compound 2.

[0046] Step 2: Preparation of compound 3.

[0047] Add dichloromethane and compound 2 to a 100L reactor, with a compound 2:dichloromethane ratio of 1g:10mL, and stir. Adjust the temperature to 30℃, and add 2M dimethylamine THF solution dropwise, with a compound 2:2M dimethylamine THF solution ratio of 1g:0.1mL, maintaining the temperature at 30℃. After the addition is complete, stir at 30℃ for 16 hours. Take 1ml of the reaction solution and perform HPLC analysis to determine that the ratio of compound 2 to compound 4 is ≤1%. After the reaction is complete, concentrate under reduced pressure at 40℃ until no distillate remains. Extract with ethyl acetate and water, collect the upper organic phase, and extract again with saturated sodium chloride aqueous solution.

[0048] The organic phase was transferred to a reaction vessel and stirred. The temperature was adjusted to 30°C, and L-DTTA (L-di-p-methylbenzoyl tartaric acid, 1.0 eq) was added. Stirring was continued for 1 hour. As stirring continued, solids gradually precipitated. The reaction solution was filtered, and the filter cake was washed with ethyl acetate. The filter cake was transferred to a reaction vessel, and an aqueous acetone solution (5 wt% water content) was added, with a filter cake: 5 wt% water content acetone ratio of 1 g: 3 mL. The temperature was raised to 40°C, and the mixture was stirred for 2 hours. The mixture was then cooled to 20°C. The reaction solution was filtered, and the filter cake was washed with acetone. The filter cake was transferred to a vacuum oven and dried under vacuum at 50°C for 6 hours.

[0049] Step 3: Preparation of crude compound 4.

[0050] Prepare a 100L reaction vessel. Add ethyl acetate, compound 3 (1.0 eq), and purified water to the reaction flask, with a compound 3:ethyl acetate:purified water ratio of 1g:10mL:10mL and stir. Adjust the temperature to 10℃. Add a 10wt% potassium carbonate aqueous solution (5.0 eq), maintaining the temperature at 10℃. After the addition is complete, continue stirring for 20 minutes. Stop stirring, separate the layers, and collect the upper organic phase. Extract the lower aqueous phase with ethyl acetate and collect the upper organic phase. Combine the organic phases and extract twice with purified water. Collect the upper organic phase, dry it with anhydrous sodium sulfate, filter, wash the filter cake with ethyl acetate, and collect the filtrate.

[0051] Transfer the filtrate to a 100L reactor and start stirring. Adjust the temperature to 20℃. Add dropwise a 10wt% methanesulfonic acid (1.0 eq) ethyl acetate solution, maintaining the temperature at 20℃. After the addition is complete, continue stirring for at least 0.5 hours, maintaining the temperature at 20℃. Filter, collect the filter cake and transfer it to a 100L reaction flask. Add acetone with 5wt% water content, the ratio of filter cake: acetone with 5wt% water content = 1g: 5mL. Maintain the temperature at 40℃ and stir for 1 hour, then cool to 20℃. Filter, wash the filter cake with acetone, dry at 30℃ for 4 hours, then heat to 50℃ and dry for 6 hours.

[0052] Step 4: Purification of compound 4.

[0053] Prepare a 100L reactor. Add acetone with a water content of 5wt% to the reactor, then add crude compound 4 (compound 4 crude product: acetone with a water content of 5wt% = 1g: 5mL). Stir at 40℃ for 3 hours. Cool to 20℃, filter, and wash the filter cake with acetone. Collect the filter cake and dry at 50℃ for 2 hours.

[0054] Example 2 The difference between Example 2 and Example 1 is that the TBAF in step 1 is 4.5 eq, and the 3 wt% sodium hydroxide aqueous solution is used in step 3.

[0055] Example 3 The difference between Example 2 and Example 1 is that in step 4, acetone with a water content of 5 wt% is replaced with acetone with a water content of 1 wt%.

[0056] Comparative Example 1 The difference between Comparative Example 1 and Example 1 is that the amount of TBAF used in step 1 is different; Comparative Example 1 adds 2.5 eq of TBAF.

[0057] Comparative Example 2 The difference between Comparative Example 2 and Example 1 is that in step 2, the solvent used to react with dimethylamine is different; dichloromethane is replaced with IPA.

[0058] Comparative Example 3 The difference between Comparative Example 3 and Example 1 is that in step 2, the solvent used to react with dimethylamine is different; dichloromethane is replaced with THF.

[0059] Comparative Example 4 The difference between Comparative Example 4 and Example 1 is that in step 2, dimethylamine is replaced with dimethylamine di-p-methylbenzoyl tartrate.

[0060] Comparative Example 5 The difference between Comparative Example 5 and Example 1 is that in step 2, the THF solution of dimethylamine is replaced with the DCM solution of dimethylamine.

[0061] Comparative Example 6 The difference between Comparative Example 6 and Example 1 is that in step 2, the THF solution of dimethylamine is replaced with an IPA solution of dimethylamine.

[0062] Comparative Example 7 The difference between Comparative Example 7 and Example 1 is that in step 2, the THF solution of dimethylamine is replaced with an aqueous solution of dimethylamine.

[0063] Comparative Example 8 The difference between Comparative Example 8 and Example 1 is that in step 2, the THF solution of dimethylamine is replaced with the THF solution of triethylamine.

[0064] Comparative Example 9 The difference between Comparative Example 9 and Example 1 is that in step 2, L-DTTA was replaced with D-mandelic acid, and the reaction failed, with no solid precipitated.

[0065] Comparative Example 10 The difference between Comparative Example 10 and Example 1 is that in step 2, L-DTTA is replaced with L-tartaric acid.

[0066] Comparative Example 11 The difference between Comparative Example 11 and Example 1 is that in step 2, the amount of L-DTTA is changed to 0.9 eq.

[0067] Comparative Example 12 The difference between Comparative Example 12 and Example 1 is that in step 4, acetone containing 5 wt% water was replaced with acetone containing 10 wt% water.

[0068] Comparative Example 13 The difference between Comparative Example 13 and Example 1 is that in step 4, acetone containing 5 wt% water was replaced with isopropanol containing 5 wt% water.

[0069] Comparative Example 14 Comparative Example 14 was prepared using the preparation method of compound 59 described in CN111247132B: compound 51 (i.e., compound 2 of the present invention) was prepared using the method of Example 1 of the patent, and compound 59 (i.e., compound 4 of the present invention) was prepared using the method of Example 4 of the patent.

[0070] Comparative Example 15 Steps 2 and 3 of Comparative Example 15 differ from those of Example 1, in that compound 2 is directly prepared into crude compound 4, specifically as follows: Prepare a 100L reaction vessel. Add ethyl acetate, compound 2 (1.0 eq), and purified water to the reaction flask, with a compound 2:ethyl acetate:purified water ratio of 1g:50mL:50mL and stir. Adjust the temperature to 10℃. Add a 10wt% potassium carbonate aqueous solution (5.0 eq), maintaining the temperature at 10℃. After the addition is complete, continue stirring for 20 minutes. Stop stirring, separate the layers, and collect the upper organic phase. Extract the lower aqueous phase with ethyl acetate and collect the upper organic phase. Combine the organic phases and extract twice with purified water. Collect the upper organic phase, dry it with anhydrous sodium sulfate, filter, wash the filter cake with ethyl acetate, and collect the filtrate.

[0071] Transfer the filtrate to a 100L reactor and start stirring. Adjust the temperature to 20℃. Add dropwise a 10wt% methanesulfonic acid (1.0 eq) solution in ethyl acetate, maintaining the temperature at 20℃. After the addition is complete, continue stirring for at least 0.5 hours, maintaining the temperature at 20℃. Filter, collect the filter cake and transfer it to a 100L reaction flask. Add 5wt% acetone (water content), with a filter cake:3wt% acetone (water content) ratio of 1g:5mL. Maintain the temperature at 40℃ and stir for 1 hour, then cool to 20℃. Filter, wash the filter cake with acetone, dry at 30℃ for 4 hours, then heat to 50℃ and dry for 6 hours.

[0072] II. Examples of Results 1. Compound 4 contains three chiral centers, and contains isomer impurities and common impurities. The purity after preparation was determined by HPLC, and the isomer content after steps 2, 3 and 4 was determined by chiral HPLC.

[0073] Purity (%) = Peak area of ​​compound 4 / Total peak area × 100%.

[0074] Isomer content (%) = Peak area of ​​isomer / Total peak area × 100%.

[0075] 2. Calculate the yields of Examples 1-3 and Comparative Examples 1-15 using the formula: Yield = Actual Product Mass / Theoretical Product Mass × 100%.

[0076] The experimental results of Examples 1-3 and Comparative Examples 1-15 are shown in Table 1.

[0077] Table 1

[0078] Note: The isomer content of compound 51 (i.e., compound 2 of the present invention) during the preparation process of Comparative Example 14 and compound 59 (i.e., compound 4 of the present invention) after column chromatography was detected. The results were: the isomer content of compound 51 was 7.32% and the isomer content of compound 59 was 5.92%.

[0079] In Examples 1-3 of this invention, through specific reaction steps, reaction reagents, reagent dosages, and purification methods, the purity and yield of compound 4 are improved, and the content of isomers is reduced.

[0080] In Comparative Example 1, changing the amount of TBAF added in step 1 resulted in a decrease in the purity and yield of compound 4.

[0081] Comparative Examples 2-3 and 5-8 changed the type of THF solution of dimethylamine in step 2, resulting in a decrease in the purity and yield of compound 4, and an increase in the content of isomers during the preparation process and in the final product.

[0082] Comparative Example 4 changed the type of THF solution for dimethylamine in step 2. Although the content of isomers was low, the yield decreased significantly.

[0083] Comparative Examples 9-11 changed the type or amount of L-DTTA in step 2. In Comparative Example 9, step 2 of the reaction failed, no solid was precipitated, and the reaction could not continue. The yield and purity of Comparative Examples 10-11 decreased.

[0084] Comparative Examples 12-13 changed the recrystallization solvent in step 4, and the final product had a higher content of isomers.

[0085] Comparative Example 14 is a prior art method for preparing compound 4, which has a low yield, a high content of isomers during the preparation process, and a high content of isomers in the final product.

[0086] Comparative Example 15 did not use L-DTTA and directly prepared compound 2 into crude compound 4. The yield was low, the content of isomers was high during the preparation process, and the content of isomers was high in the final product.

[0087] 3. Compound 4 from Example 1 was subjected to PXRD testing, and the test results are shown in [Figure 1]. Figure 1 .

[0088] The test conditions are as follows: Instrument: Bruker D8 advance; Operating status: 40kV, 40mA; Scan type: locked coupling; Increment: 0.02°; Scan range: 3°-40°; Scan speed: 0.1s / step.

[0089] Figure 1 The 2T values ​​from left to right are: 8.632, 9.395, 10.316, 10.917, 11.925, 12.344, 12.689, 13.466, 13.932, 15.252, 15.494, 16.153, 16.512, 16.717, 17.159, 17.662, 17.974, 18.520, 19.402, 19.643, 20.506, 21.389, 21.850, 22 .069, 22.831, 23.416, 24.194, 24.519, 24.859, 25.514, 25.799, 26.379, 26.740, 27.164, 28.210, 28.650, 29.107, 30.066, 30.349, 31.052, 31.655, 32.077, 32.598, 33.078, 33.476, 34.194, 35.968, 37.993.

[0090] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A method for preparing a tetrahydronaphtho[1,2-b]furan-2(3H)-one compound, characterized in that, Includes the following steps: (1) Compound 1 was reacted with tetra-n-butylammonium fluoride to obtain compound 2; (2) Compound 2 reacts with a base and L-DTTA to give compound 3; (3) Compound 3 reacts with methanesulfonic acid to give crude tetrahydronaphtho[1,2-b]furan-2(3H)-one; (4) The crude product of tetrahydronaphtho[1,2-b]furan-2(3H)-one compound was purified to obtain tetrahydronaphtho[1,2-b]furan-2(3H)-one compound; Compound 1 is: Compound 2 is: Compound 3 is: The tetrahydronaphtho[1,2-b]furan-2(3H)-one compound is: .

2. The preparation method according to claim 1, characterized in that, In step (1), the molar ratio of compound 1 and tetra-n-butylammonium fluoride is 1:(3-4.5); and / or The reaction described in step (1) is as follows: Compound 1 and tetra-n-butylammonium fluoride react at 20-30℃ for 2-4 hours.

3. The preparation method according to claim 1, characterized in that, The base mentioned in step (2) is dimethylamine.

4. The preparation method according to claim 3, characterized in that, The solvent for the dimethylamine is tetrahydrofuran.

5. The preparation method according to claim 1, characterized in that, The molar ratio of compound 2 and L-DTTA in step (2) is 1:(1-1.5).

6. The preparation method according to claim 1, characterized in that, The solvent for the reaction in step (2) is dichloromethane.

7. The preparation method according to claim 1, characterized in that, The reaction described in step (2) is as follows: compound 2 is first reacted with a base at 20-30℃ for 10-20h, and then L-DTTA is added and reacted at 20-30℃ for 1-2h.

8. The preparation method according to claim 1, characterized in that, The reaction described in step (3) is as follows: compound 3 is extracted with an inorganic base and the organic phase is collected. The organic phase is then reacted with methanesulfonic acid at 20-30℃ for 0.5-2h. The inorganic base is at least one of sodium hydroxide, potassium carbonate, potassium hydroxide, and sodium carbonate.

9. The preparation method according to claim 1, characterized in that, The purification in step (4) is recrystallization.

10. The preparation method according to claim 9, characterized in that, The solvent for recrystallization is acetone containing 1-5 wt% water.

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