A method for synthesizing 2-hydroxy-2-methylcyclopentanone compounds

Abstract

The application relates to a synthesis method of 2-hydroxy-2-methylcyclopentanone compounds and belongs to the technical field of organic synthesis. The 2-hydroxy-2-methylcyclopentanone compounds are prepared from cyclobutanone compounds through protection of carbonyl groups, deprotection and rearrangement reaction; the application does not need to use expensive metal catalysts, has mild reaction conditions, does not need high-pressure equipment, is high in safety and easy to be industrialized, is high in atomic economy, is simple in operation, avoids use of highly toxic or high-pollution reagents, and is low in mercury salt consumption.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology and relates to a method for synthesizing 2-hydroxy-2-methylcyclopentanone compounds. Background Technology

[0002] 2-Hydroxy-2-methylcyclopentanone compounds are important organic synthesis intermediates (References: WO2025 / 168043, 2025, A1; Organic Process Research and Development, 2022, vol.26, #3, 879-890), with broad application prospects in the fields of pharmaceuticals, fragrances, and natural product synthesis. These compounds possess both hydroxyl and ketone carbonyl functional groups, exhibiting a unique structure that allows them to participate in various types of organic transformation reactions.

[0003] The existing synthetic methods for 2-hydroxy-2-methylcyclopentanone compounds have the following shortcomings: 1. Numerous side reactions and low yields; 2. Common synthetic methods typically employ expensive metal catalysts, which are not conducive to industrial application and environmental protection, such as [(1,1'-biphenyl-2-yl)di-tert-butylphosphine]gold(I) chloride and silver hexafluoroantimonate (References: Advanced Synthesis and Catalysis, 2014, vol.356, #18, 3749-3754; Tetrahedron, 2012, vol.68, #26, 5241-5247; Tetrahedron Letters, 2000, vol.41, #50, 9725-9730); 3. Existing synthetic methods have limited routes and lack flexibility, failing to meet the diverse needs of different production scales and purity requirements.

[0004] Therefore, there is an urgent need to develop a simple, mild, low-cost, and environmentally friendly method for synthesizing 2-hydroxy-2-methylcyclopentanone compounds. Summary of the Invention

[0005] The purpose of this invention is to provide a method for synthesizing 2-hydroxy-2-methylcyclopentanone compounds. The method provided does not require expensive metal catalysts, has mild reaction conditions, does not require high-pressure equipment, has high atom economy, is simple to operate, avoids the use of highly toxic or polluting reagents, and requires a small amount of mercury salt.

[0006] The objective of this invention can be achieved through the following technical solutions: On one hand, the present invention provides a method for synthesizing 2-hydroxy-2-methylcyclopentanone compounds, comprising the following steps: S1.1. Reaction of cyclobutanone compounds with trimethylsilylacetylene and n-butyllithium yields compound A2; S1.2. Compound A2 is reacted with potassium carbonate to obtain compound A3; S1.3. Compound A3 is reacted with mercuric sulfate to obtain the 2-hydroxy-2-methylcyclopentanone compound; The structural formula of the cyclobutanone compounds is shown below: R1 and R2 are one of hydrogen, alkyl, phenyl and substituted phenyl; The structural formula of compound A2 is shown below: R1 and R2 are one of hydrogen, alkyl, phenyl and substituted phenyl; The structural formula of the 2-hydroxy-2-methylcyclopentanone compounds is shown below: R1 and R2 are one of hydrogen, alkyl, phenyl and substituted phenyl.

[0007] The synthesis route is as follows:

[0008] As a preferred embodiment of the present invention, compound A3 reacts with benzoyl chloride under alkaline conditions to obtain compound B2, compound B2 reacts with mercuric sulfate under nitrogen conditions to prepare compound B3, and compound B3 reacts with potassium carbonate to obtain the 2-hydroxy-2-methylcyclopentanone compound. The structural formula of compound B2 is shown below: R1 and R2 are one of hydrogen, alkyl, phenyl and substituted phenyl; The structural formula of compound B3 is shown below: R1 and R2 are one of hydrogen, alkyl, phenyl and substituted phenyl.

[0009] The synthesis route is as follows:

[0010] On the other hand, the present invention also provides a method for synthesizing 2-hydroxy-2-methylcyclopentanone compounds, comprising the following steps: S2.1. Reaction of cyclobutanone compounds with tert-butyllithium and vinyl diethyl ether yields compound C2; S2.2. Compound C2 is acidified with hydrochloric acid, resulting in ring expansion and rearrangement to obtain the 2-hydroxy-2-methylcyclopentanone compounds. The structural formula of the cyclobutanone compounds is shown below: R1 and R2 are one of hydrogen, alkyl, phenyl and substituted phenyl; The structural formula of compound C2 is shown below: R1 and R2 are one of hydrogen, alkyl, phenyl and substituted phenyl; The structural formula of the 2-hydroxy-2-methylcyclopentanone compounds is shown below: R1 and R2 are one of hydrogen, alkyl, phenyl and substituted phenyl.

[0011] The synthesis route is as follows:

[0012] As a preferred embodiment of the present invention, in step S1.1, the molar ratio of the cyclobutanone compound to trimethylsilylacetylene and n-butyllithium is 1:(1.0~1.5):(1.0~1.5).

[0013] As a preferred embodiment of the present invention, in step S1.2, the molar ratio of compound A2 to potassium carbonate is 1:(1.0~3.0), and the reaction solvent is methanol or a methanol / water mixture.

[0014] As a preferred embodiment of the present invention, in step S1.3, the molar ratio of compound A3 to mercuric sulfate is 1:(0.02~0.05), and the reaction solvent is a mixture of acetone and water with a volume ratio of 10:1.

[0015] As a preferred embodiment of the present invention, the molar ratio of compound A3, benzoyl chloride and base is 1:(1.0~2.0):(1.5~3.0), and the base is one of triethylamine, pyridine and 4-dimethylaminopyridine.

[0016] As a preferred embodiment of the present invention, the molar ratio of compound B2 to mercuric sulfate is 1:(0.02~0.05), and the molar ratio of compound B3 to potassium carbonate is 1:(1.0~3.0).

[0017] As a preferred embodiment of the present invention, in step S2.1, the molar ratio of the cyclobutanone compound to tert-butyllithium and vinyl ethyl ether is 1:(1.5~2.0):(2.0~5.0).

[0018] As a preferred embodiment of the present invention, the structural formula of compound A3 is shown below: R1 and R2 are one of hydrogen, alkyl, phenyl and substituted phenyl.

[0019] The beneficial effects of this invention are: This invention provides a method for synthesizing 2-hydroxy-2-methylcyclopentanone compounds. Using cyclobutanone compounds as starting materials, the starting material cyclobutanone compounds can undergo nucleophilic addition to the carbonyl group via α-lithiation of vinyl ethers and lithiation reagents. The resulting intermediate is then subjected to acid hydrolysis upon heating, followed by an acid-catalyzed Wagner-Meerwein rearrangement process. Under the action of acid, the alcohol hydroxyl group is protonated to form a desirable leaving group, thereby generating a highly active carbocation in situ. The adjacent carbon atoms on the ring (with their substituents) undergo 1,2-migration, yielding a thermodynamically more stable five-membered ring ketone product, namely the target product 2-hydroxy-2-methylcyclopentanone compounds.

[0020] On the other hand, the cyclobutanone compounds of the present invention can also be obtained by first reacting trimethylsilylacetylene and n-butyllithium, using a highly active alkynyllithium nucleophile to perform a nucleophilic addition reaction on cyclobutanone. The TMS group is removed in a subsequent step, which protects the alkyne bond in the first step and avoids dimerization or side reactions under strongly alkaline conditions. Then, desilylation is carried out by alkaline hydrolysis to obtain a terminal alkyne alcohol. Finally, the target product, 2-hydroxy-2-methylcyclopentanone compounds, is obtained by mercury-catalyzed rearrangement of the alkyne alcohol. Simultaneously, the alkyne alcohol obtained above can also be reacted with benzoyl chloride for benzoic acid esterification, which protects the hydroxyl group and avoids unnecessary side reactions by the free hydroxyl group in the subsequent mercury salt catalytic step. Then, hydrolysis of the ester is performed for deprotection to obtain the target product, 2-hydroxy-2-methylcyclopentanone compounds.

[0021] This invention does not require expensive metal catalysts, has mild reaction conditions, does not require high-pressure equipment, is highly safe, and is easy to scale up industrially; it also has high atom economy, is simple to operate, avoids the use of highly toxic or polluting reagents, and requires a small amount of mercury salt. Attached Figure Description

[0022] To facilitate understanding by those skilled in the art, the present invention will be further described below with reference to the accompanying drawings.

[0023] Figure 1 This is a synthetic route diagram of the present invention; Figure 2 This is the mass spectrum of compound A4; Figure 3 The image shows the proton NMR spectrum of compound A4. Figure 4 The image shows the 1H NMR spectrum of compound D4. Figure 5 This is the mass spectrum of compound D4; Figure 6 This is the 1H NMR spectrum of compound A3. Detailed Implementation

[0024] To further illustrate the technical means and effects of the present invention in achieving its intended purpose, the following detailed description of the specific implementation methods, structures, features, and effects of the present invention, in conjunction with embodiments, is provided below.

[0025] It should be noted that, unless otherwise specified, the present invention does not specifically limit the source of the raw materials used in the following embodiments. Commercially available products or products prepared by conventional preparation methods that are well known to those skilled in the art can be used. Experimental methods that do not specify specific conditions are all conventional methods and conventional conditions well known in the art.

[0026] Example 1

[0027] Starting with cyclobutanone as raw material A1:

[0028] Preparation of compound A2: 1 L of THF and 117.6 g of trimethylsilylacetylene (1.2 mol, 1.2 eq) were added to a 2 L three-necked flask. Under nitrogen protection, the mixture was cooled to -78 °C, and 750 mL of 1.6 M n-butyllithium was added dropwise. The mixture was reacted at -78 °C for 45 min. 150 mL of THF solution containing 70.0 g of compound A1 (1.0 mol, 1.0 eq) was added dropwise. The mixture was kept at this temperature for 1 h, allowed to rise naturally to 0 °C, and then quenched by adding 200 mL of ammonium chloride solution. 1000 mL of water was added, and the mixture was stirred and separated. The mixture was extracted once with 500 mL of methyl tert-butyl ether, washed with saturated brine, dried, concentrated, and then distilled under reduced pressure using an oil pump to obtain 90.0 g of compound A2, with a yield of 49%.

[0029] The NMR characterization of compound A2 is as follows: 1 H-NMR (400MHz, CDCl3): δ 0.1 (s, 9H), 1.70-1.77 (m, 2H), 2.12-2.19 (m, 2H), 2.30-2.38 (m, 2H).

[0030] Preparation of compound A3: 20.0 g of compound A2 (0.11 mol), 200 mL of methanol, and 37.8 g of potassium carbonate (0.27 mol) were added to a 500 mL single-necked flask. The mixture was reacted at 20 °C for 2 h, filtered and concentrated (water temperature 35 °C), and water and dichloromethane were added. After stirring and separation, the mixture was extracted twice with dichloromethane. The organic phases were combined, dried, concentrated, and distilled under reduced pressure to obtain a colorless liquid compound A3 with a yield of 66.2%.

[0031] The NMR characterization of compound A3 is as follows: 1H-NMR (400MHz, CDCl3): δ 1.78-1.86 (m, 2H), 2.22-2.31 (m, 2H), 2.40-2.49 (m, 2H), 2.54 (s, 1H).

[0032] Preparation of compound A4: 5.0 g of A3 (52 mmol), 55 mL of acetone / water mixed solvent (10:1 v / v), and 0.75 g of mercuric sulfate (2.6 mmol) were added to a 100 mL three-necked flask. The mixture was heated to 60 °C and reacted for 3 h. The solution was concentrated, dissolved in dichloromethane, filtered through diatomaceous earth, diluted with water, washed with sodium bicarbonate solution, dried and concentrated with saturated sodium chloride solution to obtain 5.6 g of crude product. Column chromatography yielded 2.3 g of colorless liquid, namely compound A4, with a yield of 38.9%.

[0033] NMR characterization of compound A4: 1 H-NMR (400MHz, DMSO): δ 1.09 (s, 3H), 1.69-1.86 (m, 4H), 2.16-2.21 (m, 2H), 5.14 (s, 1H).

[0034] Example 2

[0035] Starting with cyclobutanone as the starting material A1, B1 is compound A3, and B4 is compound A4. The preparation steps for B1 are the same as in Example 1:

[0036] Preparation of compound B2: 20.6 g of B1 (0.21 mol), 200 mL of DCM, and 43.3 g of TEA (0.42 mol) were added to a 500 mL three-necked flask. The mixture was cooled to 0 °C, and then 8.4 g of benzoyl chloride (0.32 mol) was added dropwise. The mixture was reacted at room temperature for 2 h, concentrated, and then methyl tert-butyl ether and water were added. The mixture was separated, dried, and concentrated. A mixed solvent of 3% ethyl acetate and 97% petroleum ether was used as the eluent for column chromatography. 16.5 g of liquid, namely compound B2, was obtained, with a yield of 39.2%.

[0037] NMR characterization of compound B2: 1 H-NMR (400MHz, CDCl3): δ 1.92-2.11(m, 2H), 2.52-2.60(m, 2H), 2.62(s, 1H), 2.68-2.75(m, 2H), 7.41-7.45(m, 2H), 7.53-7.58(m, 1H), 8.03-8.05(m, 2H).

[0038] Preparation of compound B3: 16.5 g of B2 (0.08 mol), 160 mL of acetone / water, 16 mL of acetone / water, and 1.22 g of mercuric sulfate were added to a 500 mL single-necked flask. The mixture was heated to 70 °C and reacted for 3 h under nitrogen protection. After cooling to room temperature, the mixture was concentrated, and 200 mL each of water and methyl tert-butyl ether were added. The mixture was separated, washed with sodium bicarbonate solution, dried, concentrated, and passed through a silica gel pad (MTBE) to give 17.0 g of colorless liquid, namely compound B3, with a yield of 97.7%.

[0039] NMR characterization of compound B3: 1 H-NMR (400MHz, CDCl3): δ 1.87-2.00 (m, 2H), 2.13 (s, 3H), 2.35-2.43 (m, 2H), 2.68-2.74 (m, 2H), 7.46-7.49 (m, 2H), 7.58-7.43 (m, 1H), 8.07-8.10 (m, 2H).

[0040] Preparation of compound B4: 4.7 g of B3 (21.5 mmol), 50 mL of methanol, and 5.9 g of potassium carbonate (43.1 mmol) were added to a 100 mL three-necked flask and reacted at room temperature for 2 h. The mixture was filtered, concentrated, and 100 mL each of water and dichloromethane were added. The mixture was separated, extracted three times with dichloromethane, and the organic phases were combined, washed with saturated sodium chloride solution, dried, concentrated, and subjected to column chromatography to give 1.1 g of compound B4, with a yield of 45.8%.

[0041] NMR characterization of compound B3: 1 H-NMR (400MHz, DMSO): δ 1.09 (s, 3H), 1.69-1.86 (m, 4H), 2.16-2.21 (m, 2H), 5.14 (s, 1H).

[0042] Example 3

[0043] The synthetic route using cyclobutanone as the starting material C1 is as follows:

[0044] Preparation of compound C2: 93.5 g of vinyl ethyl ether (1.3 mol) and 500 mL of THF were added to a 2 L three-necked flask. Under nitrogen protection, the mixture was cooled to -78 °C, and 500 mL of 1.3 M tert-butyllithium (0.65 mol) was added dropwise. The mixture was then naturally heated to 0 °C, cooled to -78 °C, and 30.3 g of compound C1 (0.43 mol) was added dropwise. The mixture was then naturally heated to RT and reacted for 2 h. The mixture was cooled to 0 °C, quenched with 200 mL of ammonium chloride, concentrated, and then 1000 mL of water and 1000 mL of ethyl acetate were added. The mixture was stirred, separated, and extracted once with ethyl acetate. The organic phases were combined, washed with saturated brine, dried, concentrated, and distilled under reduced pressure to obtain 43.8 g of compound C2.

[0045] Preparation of compound C3: 200 mL of diethyl ether, 0.308 mol of compound C2 (43.8 mol), and 200 mL of 0.1 M hydrochloric acid were added to a 1 L three-necked flask and reacted at room temperature for 2 h. The mixture was separated, extracted three times with dichloromethane, and the organic phases were combined, dried, concentrated, and distilled twice under reduced pressure using a water pump to obtain 5.2 g of colorless liquid, namely compound C3, with a yield of 10.6%.

[0046] NMR characterization of compound C3: 1 H-NMR (400MHz, DMSO): δ 1.09 (s, 3H), 1.69-1.86 (m, 4H), 2.16-2.21 (m, 2H), 5.14 (s, 1H).

[0047] Example 4

[0048] Starting with 3-phenylcyclobutanone as raw material D1:

[0049] Preparation of compound D2: 250 mL of THF and 20.1 g of trimethylsilylacetylene (0.20 mol) were added to a 500 mL three-necked flask. Under nitrogen protection, the mixture was cooled to -78 °C, and 82.1 mL of 2.5 M n-butyllithium (0.20 mol) was added dropwise. The mixture was reacted at -78 °C for 45 min, and 50 mL of THF solution containing 25.0 g of compound D1 (0.17 mol) was added dropwise. The mixture was kept at this temperature for 1 h, allowed to rise naturally to 0 °C, and quenched by adding 100 mL of ammonium chloride solution. 200 mL of water was added, and the mixture was stirred and separated. The mixture was extracted once with methyl tert-butyl ether, washed with saturated sodium chloride solution, dried, concentrated, and subjected to column chromatography (PE:EA = 50:1-20:1) to obtain 36.0 g of compound D2, with a yield of 86.7%.

[0050] NMR characterization of compound D2: 1H-NMR (400MHz, CDCl3): δ 0.2 (s, 9H), 2.34-2.40 (m, 2H), 2.64-2.89 (m, 2H), 3.28-3.30 (m, 1H), 6.17-7.25 (m, 3H), 7.28-7.32 (m, 2H).

[0051] Preparation of compound D3: 36.0 g D2 (0.147 mol), 360 mL methanol, and 50.9 g potassium carbonate (0.368 mol) were added to a 1 L three-necked flask and reacted at room temperature for 2 h. The mixture was filtered and concentrated, and 200 mL each of water and dichloromethane were added. The mixture was stirred and separated, and extracted twice with dichloromethane. The organic phases were combined, dried, and concentrated to obtain 24.9 g of solid, namely compound D3, with a yield of 98.8%.

[0052] NMR characterization of compound D3: 1 H-NMR (400MHz, CDCl3): δ 2.36-2.43(m, 2H), 2.58 (s, 1H), 2.86-2.92(m, 2H), 3.28-3.37(m, 1H), 7.18-7.25(m, 3H), 7.29-7.31(m, 2H).

[0053] Preparation of compound D4: 4.9 g of compound D3 (0.144 mol), acetone / water = 250 ml / 25 ml, and 2.1 g of mercuric sulfate (0.007 mol) were added to a 500 mL single-necked flask. Under nitrogen protection, the mixture was heated to 70 °C and reacted for 3 h. The mixture was then cooled, concentrated, and column chromatography was performed to obtain 19.0 g of white solid, namely compound D4, with a yield of 65.6%.

[0054] NMR characterization of compound D4: 1 H-NMR (400MHz, CDCl3): δ 1.37-1.39 (d, 3H), 1.86-1.92 (m, 0.5H), 2.10-2.17 (m, 0.5H), 2.39-2.54 (m, 2H), 2.83-2.91 (m, 1H), 3.31-3.34 (m, 0.5H), 3.62-3.68 (m, 0.5H), 1.86-1.92 (m, 0.5H), 7.23-7.26 (m, 3H), 7.32-7.36 (m, 2H).

[0055] Example 5

[0056] Starting with 3-phenylcyclobutanone E1:

[0057] Preparation of compound E2: 14.8 g of vinyl ethyl ether (0.205 mol) and 100 mL of THF were added to a 500 mL three-necked flask. Under nitrogen protection, the mixture was cooled to -78 °C, and 79 mL of 1.3 M tert-butyllithium (0.102 mol) was added dropwise. The mixture was then naturally heated to 0 °C, cooled to -78 °C, and 10.0 g of compound E1 (0.068 mol) was added dropwise. The mixture was naturally heated to room temperature for 2 h, cooled to 0 °C, and quenched with 100 mL of ammonium chloride. The mixture was concentrated, and 100 mL of water and 100 mL of ethyl acetate were added. The mixture was stirred, separated, and extracted once with ethyl acetate. The organic phases were combined, washed with saturated brine, dried, concentrated, and column chromatography was used to obtain 5.3 g of compound E2.

[0058] Preparation of compound E3: 50 mL of THF, 5.3 g of compound E2 (0.024 mol), and 50 mL of 0.1 M hydrochloric acid were added to a 250 mL three-necked flask and reacted at room temperature for 4 h. After separation and extraction with dichloromethane three times, the organic phases were combined, dried, concentrated, and subjected to column chromatography to obtain 1.8 g of compound E3. The two-step yield was 13.9%.

[0059] NMR characterization of compound E3: 1 H-NMR (400MHz, CDCl3): δ 1.37-1.39(d, 3H), 1.86-1.92(m, 0.5H), 2.10-2.17(m, 0.5H), 2.39-2.54(m, 2H), 2.83-2.91(m, 1H), 3 .31-3.34(m, 0.5H), 3.62-3.68(m, 0.5H), 1.86-1.92(m, 0.5H), 7.23-7.26(m, 3H), 7.32-7.36(m, 2H).

[0060] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A method for synthesizing 2-hydroxy-2-methylcyclopentanone compounds, characterized in that, Includes the following steps: S1.

1. Reaction of cyclobutanone compounds with trimethylsilylacetylene and n-butyllithium yields compound A2; S1.

2. Compound A2 is reacted with potassium carbonate to obtain compound A3; S1.

3. Compound A3 is reacted with mercuric sulfate to obtain the 2-hydroxy-2-methylcyclopentanone compound; The structural formula of the cyclobutanone compounds is shown below: R1 and R2 are one of hydrogen, alkyl, phenyl and substituted phenyl; The structural formula of compound A2 is shown below: R1 and R2 are one of hydrogen, alkyl, phenyl and substituted phenyl; The structural formula of the 2-hydroxy-2-methylcyclopentanone compounds is shown below: R1 and R2 are one of hydrogen, alkyl, phenyl and substituted phenyl.

2. The method for synthesizing 2-hydroxy-2-methylcyclopentanone compounds according to claim 1, characterized in that, The compound A3 reacts with benzoyl chloride under alkaline conditions to give compound B2. Compound B2 reacts with mercuric sulfate under nitrogen conditions to prepare compound B3. Compound B3 reacts with potassium carbonate to give the 2-hydroxy-2-methylcyclopentanone compound. The structural formula of compound B2 is shown below: R1 and R2 are one of hydrogen, alkyl, phenyl and substituted phenyl; The structural formula of compound B3 is shown below: R1 and R2 are one of hydrogen, alkyl, phenyl and substituted phenyl.

3. A method for synthesizing 2-hydroxy-2-methylcyclopentanone compounds, characterized in that, Includes the following steps: S2.

1. Reaction of cyclobutanone compounds with tert-butyllithium and vinyl diethyl ether yields compound C2; S2.

2. Compound C2 is acidified with hydrochloric acid, resulting in ring expansion and rearrangement to obtain the 2-hydroxy-2-methylcyclopentanone compounds. The structural formula of the cyclobutanone compounds is shown below: R1 and R2 are one of hydrogen, alkyl, phenyl and substituted phenyl; The structural formula of compound C2 is shown below: R1 and R2 are one of hydrogen, alkyl, phenyl and substituted phenyl; The structural formula of the 2-hydroxy-2-methylcyclopentanone compounds is shown below: R1 and R2 are one of hydrogen, alkyl, phenyl and substituted phenyl.

4. The method for synthesizing 2-hydroxy-2-methylcyclopentanone compounds according to claim 1, characterized in that, In step S1.1, the molar ratio of the cyclobutanone compound to trimethylsilylacetylene and n-butyllithium is 1:(1.0~1.5):(1.0~1.5).

5. The method for synthesizing 2-hydroxy-2-methylcyclopentanone compounds according to claim 1, characterized in that, In step S1.2, the molar ratio of compound A2 to potassium carbonate is 1:(1.0~3.0), and the reaction solvent is methanol or a methanol / water mixture.

6. The method for synthesizing 2-hydroxy-2-methylcyclopentanone compounds according to claim 1, characterized in that, In step S1.3, the molar ratio of compound A3 to mercuric sulfate is 1:(0.02~0.05), and the reaction solvent is a mixture of acetone and water with a volume ratio of 10:

1.

7. The method for synthesizing 2-hydroxy-2-methylcyclopentanone compounds according to claim 2, characterized in that, The molar ratio of compound A3, benzoyl chloride, and base is 1:(1.0~2.0):(1.5~3.0), and the base is one of triethylamine, pyridine, and 4-dimethylaminopyridine.

8. The method for synthesizing 2-hydroxy-2-methylcyclopentanone compounds according to claim 1, characterized in that, The molar ratio of compound B2 to mercuric sulfate is 1:(0.02~0.05), and the molar ratio of compound B3 to potassium carbonate is 1:(1.0~3.0).

9. The method for synthesizing 2-hydroxy-2-methylcyclopentanone compounds according to claim 3, characterized in that, In step S2.1, the molar ratio of the cyclobutanone compound to tert-butyllithium and vinyl ethyl ether is 1:(1.5~2.0):(2.0~5.0).

10. The method for synthesizing 2-hydroxy-2-methylcyclopentanone compounds according to claim 1 or 2, characterized in that, The structural formula of compound A3 is shown below: R1 and R2 are one of hydrogen, alkyl, phenyl and substituted phenyl.

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