Method for preparing optically active 2-fluoropropionate

Abstract

The invention discloses a method for preparing optically active 2-fluoropropionate. The method comprises the following steps: step 1, preparing nitrobenzenesulfonyl fluoride; step 2, synthesizing 2-fluoropropionate with optical activity; the raw material nitrobenzenesulfonyl chloride can be conveniently prepared through a sulfonation reaction of substituted aromatic hydrocarbon, potassium fluoride, (S)-(-)-lactate and the like are commercialized bulk chemicals, the purchase channel is wide, the price is low, and the industrial production cost is remarkably reduced. According to the method, the use of a dangerous fluorinating reagent HF is avoided, and the reaction solvent can be recycled and reused; the water phase generated in the reaction in the first step can be recycled after potassium fluoride is supplemented, and the nitrobenzene sulfonate byproduct generated in the reaction in the second step can be recycled for preparing nitrobenzene sulfonyl chloride, so that the resource circulation is realized, and the emission of three wastes is greatly reduced.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, specifically to a method for preparing optically active 2-fluoropropionate. Background Technology

[0002] Optically active 2-fluoropropionates are an important class of chiral organic intermediates, widely used in the synthesis of herbicides, pharmaceuticals, and fine chemicals. Among them, chiral methyl 2-fluoropropionate, as a key intermediate in the preparation of highly efficient herbicides, has been a research hotspot in the field of organic synthesis due to its green synthesis methods, high yields, and high enantioselectivity.

[0003] Currently, existing methods for preparing optically active 2-fluoropropionates have many shortcomings:

[0004] The literature (Alkali Metal Fluorides as Efficient Fluorinating Agents. Enantiocontrolled Synthesis of 2-Fluoroalkyl Carboxylates and 1-Fluoroalkyl Benzenes. CN101528662A.WO2015164643A1.) describes the reaction of (S)-(-)-lactic acid methyl ester with methanesulfonyl chloride to produce (S)-2-methanesulfonyloxycarboxylic acid methyl ester, which is then reacted with potassium fluoride in formamide to obtain (R)-2-fluoropropionate methyl ester (80.5%). This route has poor atom economy, generates a large amount of waste, and produces 2-chloropropionate methyl ester, a Class II genotoxic impurity that is harmful to human health and the environment.

[0005] Another preparation method (US200871108A1) uses (S)-(-)-lactic acid methyl ester as a raw material, which generates (S)-2-thionyl chloride oxypropionate methyl ester in the presence of thionyl chloride. This methyl ester is then reacted with HF to obtain (S)-2-thionyl chloride oxypropionate methyl ester, which is then decomposed by heating to yield (R)-2-fluoropropionate methyl ester. This route involves many steps and uses hazardous reagents such as HF, with a yield of 38% and an ee of 96.3%.

[0006] Patent CN112079755A reports a method using (S)-(-)-lactic acid methyl ester as a raw material to generate (S)-2-thionyl fluoride oxypropionate methyl ester under the action of a sulfonyl fluoride group, followed by thermal decomposition to obtain (R)-2-fluoropropionate methyl ester. This route has a yield of 70% and an ee of 95%. However, this method requires stringent synthesis conditions and sophisticated equipment.

[0007] Patent CN104774152B describes the reaction of (S)-(-)-methyl lactate with thioyl fluoride in the presence of a methyl amine to produce (R)-2-fluoropropionate methyl ester. This route has a yield of 90% and an ee of 97%. It is also a sulfonyl fluoride reagent method, and the pyrolysis conditions are harsh.

[0008] Patent CN101528662A describes the process of obtaining methyl (R)-2-fluoropropionate from (S)-(-)-lactic acid ester using N,N-dimethyltetrafluoroethylamine (TFEDMA). This method has a short route and high conversion rate (yield: 83%, ee: 96%). The main problem with this method is that TFEDMA is derived from the reaction of tetrafluoroethylene and dimethylamine, which is a hazardous chemical, making transportation and use extremely inconvenient.

[0009] The literature (Effetdelaconcentrationenacidefluorhydriquedanslapyridinesurlaregio-selectivedelafluorationpardeaminationd′α-amino-esterssynthesesdecomposescargoxyles-β-fluores.) describes a route that uses ethyl 2-aminocarboxylate as a starting material, followed by diazotization and nucleophilic reactions to yield ethyl 2-fluoropropionate. This preparation requires a diazonium salt intermediate and a large amount of HF salt as a solvent, resulting in poor reaction safety and severe HF pollution.

[0010] The literature (PyFluorA Low-Cost, Stable, and Selective Deoxyfluorination Reagent. Sulfonyl Fluoride Synthesis through Electrochemical Oxidative Coupling of Thiols and Potassium Fluoride.) reports the following process: starting with 2-mercaptopyridine, pyridinesulfonyl chloride is first generated under NaOCl, then reacts with KHF2 or KF to generate pyridinesulfonyl fluoride. The pyridinesulfonyl fluoride reacts with S-methyl propionate to generate pyridinesulfonate ester, which is then reacted with DBU to yield R-methyl lactate. This route offers mild conditions, high yield, and good substrate compatibility. However, the preparation of 2-pyridinesulfonyl fluoride is difficult and costly, significantly limiting its commercialization potential.

[0011] The above seven methods for preparing 2-fluoropropionates all have certain shortcomings.

[0012] In view of the problems of high raw material hazard, large amount of waste, low yield, complex process and high cost in the existing technology, the present invention aims to provide a method for preparing optically active 2-fluoropropionate with readily available raw materials, mild conditions, green and environmentally friendly and high yield. Summary of the Invention

[0013] The purpose of this invention is to provide a method for preparing optically active 2-fluoropropionate to solve the problems mentioned in the background art.

[0014] To achieve the above objectives, the present invention provides the following technical solution: a method for preparing optically active 2-fluoropropionate, comprising the following steps:

[0015] Step 1: Preparation of nitrobenzenesulfonyl fluoride: Nitrobenzenesulfonyl chloride and potassium fluoride are added to a reaction vessel at a molar ratio of 1.0 to 4.0:1. A mixed solvent of organic solvent and water and a phase transfer catalyst are added. The reaction temperature is controlled at 20 to 80°C, and the reaction is stirred for 3 to 6 hours. After the reaction is completed, the liquid is separated, and the organic phase is treated to obtain nitrobenzenesulfonyl fluoride.

[0016] Step 2: Synthesis of optically active 2-fluoropropionate: (S)-(-)-lactic acid ester and nitrobenzenesulfonyl fluoride obtained in Step 1 are added to a reaction vessel at a molar ratio of 1:1.0-1.5, along with a styrannol and an organic solvent; the reaction temperature is controlled at 20-70℃, and the reaction is stirred for 5-20 hours. After the reaction is completed, the optically active 2-fluoropropionate is obtained through post-treatment.

[0017] Preferably, the nitrobenzenesulfonyl chloride in step one is 2-nitrobenzenesulfonyl chloride, 3-nitrobenzenesulfonyl chloride, or 4-nitrobenzenesulfonyl chloride; the molar ratio of nitrobenzenesulfonyl chloride to potassium fluoride is preferably 3:1.

[0018] Preferably, in the mixed solvent of organic solvent and water in step one, the organic solvent is selected from toluene, acetonitrile, dichloromethane, and dichloroethane, with dichloromethane being preferred; the volume ratio of organic solvent to water is 10 to 20:1.

[0019] The phase transfer catalyst is selected from one of tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate, and 18-crown-6, with tetrabutylammonium bromide being preferred; the amount of catalyst used is 0.5% to 2% of the mass of nitrobenzenesulfonyl chloride.

[0020] Preferably, the reaction temperature in step one is 25–40°C; after the reaction is complete, 1.0 eq of potassium fluoride is added to the aqueous phase for recycling in the next batch of reaction.

[0021] Preferably, the chemical reaction formula for step one is:

[0022]

[0023] Preferably, the lactate in step two is selected from one of triethylamine, DBU, DABCO, and K2CO3, with DBU being preferred; the molar ratio of (S)-(-)-lactic acid ester to lactate is preferably 1:2.

[0024] Preferably, the organic solvent in step two is selected from dichloromethane, acetonitrile, and toluene, with dichloromethane being the most preferred.

[0025] Preferably, the reaction temperature in step two is 40–50°C, and the reaction time is 10–15 h.

[0026] Preferably, the post-processing in step two includes filtration, washing, drying, concentration and distillation, and the purity of the target product, optically active 2-fluoropropionate, is ≥99%, the yield is ≥87%, and the ee value is ≥97%.

[0027] Preferably, the chemical reaction formula for step two is:

[0028]

[0029] Compared with the prior art, the beneficial effects of the present invention are:

[0030] (1) Raw materials are readily available and low cost: Nitrobenzenesulfonyl chloride, the raw material used in this invention, can be easily prepared by sulfonation reaction of substituted aromatic hydrocarbons. Potassium fluoride, (S)-(-)-lactic acid ester, etc. are all commercial bulk chemicals with wide procurement channels and low prices, which significantly reduces the cost of industrial production.

[0031] (2) Green and environmentally friendly with less waste: This invention avoids the use of dangerous fluorinating reagent HF, and the reaction solvent can be recycled; the aqueous phase generated in the first step reaction can be recycled after adding potassium fluoride, and the nitrobenzene sulfonate byproduct generated in the second step reaction can be recycled to prepare nitrobenzene sulfonyl chloride, realizing resource recycling and greatly reducing the amount of waste.

[0032] (3) Mild reaction conditions and safe operation: The reaction temperature is controlled at 20-70℃, and no high temperature and high pressure equipment is required; all reagents used are conventional chemicals, and there are no flammable, explosive or highly toxic reagents, which reduces the safety risks in the production process and facilitates industrial operation and management.

[0033] (4) High product yield and excellent quality: By optimizing the raw material ratio, solvent and reaction parameters, the target product yield can reach more than 88%, with a purity of ≥99% and an ee value of ≥97%, meeting the quality requirements of high-end intermediates.

[0034] (5) The process is highly versatile: it is applicable to the synthesis of 2-fluoropropionates with various R2 substituents, and the preparation of nitrobenzenesulfonyl fluoride can be achieved through continuous production via aqueous phase circulation, thereby improving production efficiency. Attached Figure Description

[0035] Figure 1 This is a flowchart of the method of the present invention. Detailed Implementation

[0036] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0037] Please see Figure 1 This invention provides a method for preparing optically active 2-fluoropropionate, comprising the following steps:

[0038] Step 1: Preparation of nitrobenzenesulfonyl fluoride: Nitrobenzenesulfonyl chloride and potassium fluoride are added to a reaction vessel at a molar ratio of 1.0–4.0:1, along with a mixed solvent of organic solvent and water, and a phase transfer catalyst. The reaction temperature is controlled at 20–80°C, and the mixture is stirred for 3–6 hours. After the reaction is complete, the mixture is separated, and the organic phase is treated to obtain nitrobenzenesulfonyl fluoride. The nitrobenzenesulfonyl chloride is 2-nitrobenzenesulfonyl chloride, 3-nitrobenzenesulfonyl chloride, or 4-nitrobenzenesulfonyl chloride. The preferred molar ratio of nitrobenzenesulfonyl chloride to potassium fluoride is 3:1. In the mixed solvent of organic solvent and water, the organic solvent… The solvent is selected from toluene, acetonitrile, dichloromethane, and dichloroethane, preferably dichloromethane; the volume ratio of organic solvent to water is 10-20:1; the phase transfer catalyst is selected from tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate, and 18-crown-6, preferably tetrabutylammonium bromide; the amount of catalyst used is 0.5%-2% of the mass of nitrobenzenesulfonyl chloride; the reaction temperature in step one is preferably 25-40℃; after the reaction is completed, 1.0 eq of potassium fluoride is added to the aqueous phase for recycling in the next batch of reaction; the chemical reaction formula of step one is:

[0039]

[0040] Step 2: Synthesis of optically active 2-fluoropropionate: (S)-(-)-lactic acid ester and the nitrobenzenesulfonyl fluoride obtained in Step 1 are added to a reaction vessel at a molar ratio of 1:1.0–1.5. Acid-adding agent and organic solvent are added. The reaction temperature is controlled at 20–70°C, and the reaction is stirred for 5–20 hours. After the reaction is complete, post-treatment yields optically active 2-fluoropropionate. The acid-adding agent is selected from triethylamine, DBU, DABCO, and K2CO3, with DBU being preferred. The molar ratio of (S)-(-)-lactic acid ester to acid-adding agent is preferably 1:2. The organic solvent is selected from dichloromethane, acetonitrile, and toluene, with dichloromethane being preferred. The reaction temperature is preferably 40–50°C, and the reaction time is preferably 10–15 hours. Post-treatment includes filtration, washing, drying, concentration, and distillation. The purity of the target product, optically active 2-fluoropropionate, is ≥99%, the yield is ≥87%, and the ee value is ≥97%. The chemical reaction formula for Step 2 is:

[0041]

[0042] R 1 =-NO2, -CF3, -SO2R;

[0043] R 2 = C1 to C10 alkyl or aryl groups.

[0044] Example 1: Preparation of methyl R-2-fluoropropionate using 2-nitrobenzenesulfonyl fluoride as a fluorinating agent

[0045] Step 1: Preparation of 2-nitrobenzenesulfonyl fluoride

[0046] At room temperature, 44.32 g (0.2 mol) of 2-nitrobenzenesulfonyl chloride, 600 mL of acetonitrile, and 30 mL of water were added to a 500 mL three-necked reaction flask. After stirring until homogeneous, 0.44 g (0.0016 mol) of tetrabutylammonium chloride was added, followed by the partial addition of 34.8 g (0.6 mol) of potassium fluoride. After the addition was complete, the reaction temperature was controlled at 25–30 °C, and the reaction was stirred for 4 h. GC analysis showed that the conversion rate of 2-nitrobenzenesulfonyl chloride was ≥99%, indicating the reaction was complete.

[0047] The mixture was allowed to stand and separated. The organic phase was washed twice with 100 mL of water, dried over anhydrous sodium sulfate, and concentrated to dryness to obtain crude 2-nitrobenzenesulfonyl fluoride. The crude product was then distilled under reduced pressure (0.09 MPa, distillation range 85–88 °C) to obtain 40 g of 2-nitrobenzenesulfonyl fluoride with a purity of 99.2% and a yield of 97.6%. The aqueous phase was retained for subsequent recycling.

[0048] Step 2: Synthesis of methyl R-2-fluoropropionate

[0049] Add 52 mL of dichloromethane, 10.41 g (0.1 mol) of (S)-(-)-lactic acid methyl ester, and 22.57 g (0.11 mol) of 2-nitrobenzenesulfonyl fluoride prepared in step one to a 250 mL three-necked reaction flask. After stirring until homogeneous, slowly add 0.38 g (0.2 mol) of DBU3 dropwise. After the addition is complete, control the reaction temperature at 40–45 °C and stir for 12 h. GC detection shows that the conversion rate of (S)-(-)-lactic acid methyl ester is ≥99%, indicating the reaction is complete.

[0050] Solid byproducts were removed by filtration. The filtrate was washed twice with 50 mL of water and once with 50 mL of saturated brine. After drying with anhydrous sodium sulfate, the solution was concentrated to dryness to obtain crude methyl R-2-fluoropropionate. The crude product was then distilled (vacuum 0.095 MPa, distillation range 58–60 °C) to obtain 9.8 g of pure methyl R-2-fluoropropionate with a purity of 99.1%, a yield of 88%, and an ee value of 97.5%.

[0051] Example 2: Preparation of methyl R-2-fluoropropionate using 4-nitrobenzenesulfonyl fluoride as a fluorinating agent

[0052] Step 1: Preparation of 4-nitrobenzenesulfonyl fluoride

[0053] At room temperature, 44.32 g (0.2 mol) of 4-nitrobenzenesulfonyl chloride, 600 mL of dichloromethane, and 30 mL of water were added to a 500 mL three-necked reaction flask. After stirring until homogeneous, 0.58 g (0.0018 mol) of tetrabutylammonium bromide was added, followed by the partial addition of 34.8 g (0.6 mol) of potassium fluoride. After the addition was complete, the reaction temperature was maintained at 30–35 °C, and the reaction was stirred for 4 h. GC analysis showed that the conversion rate of 4-nitrobenzenesulfonyl chloride was ≥99%, indicating the reaction was complete.

[0054] The mixture was allowed to stand and separated. The organic phase was washed twice with 100 mL of water, dried over anhydrous sodium sulfate, and concentrated to dryness to obtain crude 4-nitrobenzenesulfonyl fluoride. The crude product was then distilled under reduced pressure (0.09 MPa, distillation range 90–92 °C) to obtain 40 g of 4-nitrobenzenesulfonyl fluoride with a purity of 99.3% and a yield of 97.6%. The aqueous phase was retained for subsequent recycling.

[0055] Step 2: Synthesis of methyl R-2-fluoropropionate

[0056] Add 52 mL of dichloromethane, 10.41 g (0.1 mol) of (S)-(-)-lactic acid methyl ester, and 22.57 g (0.11 mol) of 4-nitrobenzenesulfonyl fluoride prepared in step one to a 250 mL three-necked reaction flask. After stirring until homogeneous, slowly add 0.38 g (0.2 mol) of DBU3 dropwise. After the addition is complete, control the reaction temperature at 45–50 °C and stir for 10 h. GC analysis shows that the conversion rate of (S)-(-)-lactic acid methyl ester is ≥99%, indicating the reaction is complete.

[0057] Solid byproducts were removed by filtration. The filtrate was washed twice with 50 mL of water and once with 50 mL of saturated brine. After drying with anhydrous sodium sulfate, the solution was concentrated to dryness to obtain crude methyl R-2-fluoropropionate. The crude product was then distilled (vacuum 0.095 MPa, distillation range 58–60 °C) to obtain 9.8 g of pure methyl R-2-fluoropropionate with a purity of 99.2%, a yield of 88%, and an ee value of 97.3%.

[0058] Example 3: Preparation of 4-nitrobenzenesulfonyl fluoride and methyl R-2-fluoropropionate by aqueous phase recycling

[0059] Step 1: Preparation of 4-nitrobenzenesulfonyl fluoride by aqueous phase circulation

[0060] At room temperature, 44.32 g (0.2 mol) of 4-nitrobenzenesulfonyl chloride, 600 mL of dichloromethane, and the aqueous phase retained from the first step of Example 2 were added to a 500 mL three-necked reaction flask. After stirring thoroughly, 0.58 g (0.0018 mol) of tetrabutylammonium bromide was added, followed by 11.6 g (0.2 mol) of potassium fluoride in portions. After the addition was complete, the reaction temperature was controlled at 30–35 °C, and the reaction was stirred for 4 h. GC analysis showed that the conversion rate of 4-nitrobenzenesulfonyl chloride was ≥99%, indicating the reaction was complete.

[0061] The mixture was allowed to stand and separated. The organic phase was washed twice with 100 mL of water, dried over anhydrous sodium sulfate, and concentrated to dryness to obtain crude 4-nitrobenzenesulfonyl fluoride. The crude product was then distilled under reduced pressure to obtain 39.6 g of 4-nitrobenzenesulfonyl fluoride with a purity of 99.1% and a yield of 96.6%. The aqueous phase was retained and could be recycled.

[0062] Step 2: Synthesis of methyl R-2-fluoropropionate

[0063] Following the same procedure as in Step 2 of Example 2, 9.8 g of pure methyl R-2-fluoropropionate was obtained, with a purity of 99.0%, a yield of 88%, and an ee value of 97.2%.

[0064] Example 4: Preparation of ethyl R-2-fluoropropionate using 3-nitrobenzenesulfonyl fluoride as a fluorinating agent

[0065] Step 1: Preparation of 3-nitrobenzenesulfonyl fluoride

[0066] At room temperature, 44.32 g (0.2 mol) of 3-nitrobenzenesulfonyl chloride, 600 mL of dichloromethane, and the aqueous phase retained from the first step of Example 2 were added to a 500 mL three-necked reaction flask. After stirring thoroughly, 0.58 g (0.0018 mol) of tetrabutylammonium bromide was added, followed by 11.6 g (0.2 mol) of potassium fluoride in portions. After the addition was complete, the reaction temperature was controlled at 30–35 °C, and the reaction was stirred for 4 h. GC analysis showed that the conversion rate of 3-nitrobenzenesulfonyl chloride was ≥99%, indicating the reaction was complete.

[0067] After standing and separating, the organic phase was washed twice with 100 mL of water, dried over anhydrous sodium sulfate, and concentrated to dryness to obtain crude 3-nitrobenzenesulfonyl fluoride. The crude product was then distilled under reduced pressure to obtain 39.6 g of 3-nitrobenzenesulfonyl fluoride with a purity of 99.0% and a yield of 96.6%.

[0068] Step 2: Synthesis of ethyl R-2-fluoropropionate

[0069] Add 52 mL of dichloromethane, 11.81 g (0.1 mol) of (S)-(-)-ethyl lactate, and 22.57 g (0.11 mol) of 3-nitrobenzenesulfonyl fluoride prepared in step one to a 250 mL three-necked reaction flask. After stirring until homogeneous, slowly add 0.38 g (0.2 mol) of DBU. After the addition is complete, control the reaction temperature at 40–45 °C and stir for 15 h. GC detection shows that the conversion rate of (S)-(-)-ethyl lactate is ≥99%, indicating the reaction is complete.

[0070] Solid byproducts were removed by filtration. The filtrate was washed with water and saturated brine, dried, and then concentrated to dryness to obtain crude ethyl R-2-fluoropropionate. The crude product was then distilled to obtain 11.2 g of pure ethyl R-2-fluoropropionate with a purity of 99.0%, a yield of 87.5%, and an ee value of 97.0%.

[0071] This invention:

[0072] (1) Raw materials are readily available and low cost: Nitrobenzenesulfonyl chloride, the raw material used in this invention, can be easily prepared by sulfonation reaction of substituted aromatic hydrocarbons. Potassium fluoride, (S)-(-)-lactic acid ester, etc. are all commercial bulk chemicals with wide procurement channels and low prices, which significantly reduces the cost of industrial production.

[0073] (2) Green and environmentally friendly with less waste: This invention avoids the use of dangerous fluorinating reagent HF, and the reaction solvent can be recycled; the aqueous phase generated in the first step reaction can be recycled after adding potassium fluoride, and the nitrobenzene sulfonate byproduct generated in the second step reaction can be recycled to prepare nitrobenzene sulfonyl chloride, realizing resource recycling and greatly reducing the amount of waste.

[0074] (3) Mild reaction conditions and safe operation: The reaction temperature is controlled at 20-70℃, and no high temperature and high pressure equipment is required; all reagents used are conventional chemicals, and there are no flammable, explosive or highly toxic reagents, which reduces the safety risks in the production process and facilitates industrial operation and management.

[0075] (4) High product yield and excellent quality: By optimizing the raw material ratio, solvent and reaction parameters, the target product yield can reach more than 88%, with a purity of ≥99% and an ee value of ≥97%, meeting the quality requirements of high-end intermediates.

[0076] (5) The process is highly versatile: it is applicable to the synthesis of 2-fluoropropionates with various R2 substituents, and the preparation of nitrobenzenesulfonyl fluoride can be achieved through continuous production via aqueous phase circulation, thereby improving production efficiency.

[0077] Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing optically active 2-fluoropropionate, characterized in that: Includes the following steps: Step 1: Preparation of nitrobenzenesulfonyl fluoride: Nitrobenzenesulfonyl chloride and potassium fluoride are added to a reaction vessel at a molar ratio of 1.0 to 4.0:

1. A mixed solvent of organic solvent and water and a phase transfer catalyst are added. The reaction temperature is controlled at 20 to 80°C, and the reaction is stirred for 3 to 6 hours. After the reaction is completed, the liquid is separated, and the organic phase is treated to obtain nitrobenzenesulfonyl fluoride. Step 2: Synthesis of optically active 2-fluoropropionate: (S)-(-)-lactic acid ester and nitrobenzenesulfonyl fluoride obtained in Step 1 are added to a reaction vessel at a molar ratio of 1:1.0-1.5, along with a styrannol and an organic solvent; the reaction temperature is controlled at 20-70℃, and the reaction is stirred for 5-20 hours. After the reaction is completed, the optically active 2-fluoropropionate is obtained through post-treatment.

2. The method for preparing optically active 2-fluoropropionate according to claim 1, characterized in that: The nitrobenzenesulfonyl chloride mentioned in step one is 2-nitrobenzenesulfonyl chloride, 3-nitrobenzenesulfonyl chloride or 4-nitrobenzenesulfonyl chloride; the molar ratio of nitrobenzenesulfonyl chloride to potassium fluoride is preferably 3:

1.

3. The method for preparing optically active 2-fluoropropionate according to claim 1, characterized in that: In the mixed solvent of organic solvent and water in step one, the organic solvent is selected from one of toluene, acetonitrile, dichloromethane, and dichloroethane, preferably dichloromethane; the volume ratio of organic solvent to water is 10 to 20:

1. The phase transfer catalyst is selected from one of tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate, and 18-crown-6, with tetrabutylammonium bromide being preferred; the amount of catalyst used is 0.5% to 2% of the mass of nitrobenzenesulfonyl chloride.

4. The method for preparing optically active 2-fluoropropionate according to claim 1, characterized in that: The preferred reaction temperature in step one is 25–40°C. After the reaction is complete, 1.0 eq of potassium fluoride is added to the aqueous phase for recycling in the next batch of reaction.

5. The method for preparing optically active 2-fluoropropionate according to claim 1, characterized in that: The chemical reaction formula for step one is:

6. The method for preparing optically active 2-fluoropropionate according to claim 1, characterized in that: In step two, the lactate is selected from one of triethylamine, DBU, DABCO, and K2CO3, with DBU being preferred; the molar ratio of (S)-(-)-lactic acid ester to lactate is preferably 1:

2.

7. The method for preparing optically active 2-fluoropropionate according to claim 1, characterized in that: The organic solvent used in step two is selected from dichloromethane, acetonitrile, and toluene, with dichloromethane being preferred.

8. The method for preparing optically active 2-fluoropropionate according to claim 1, characterized in that: In step two, the preferred reaction temperature is 40–50°C, and the preferred reaction time is 10–15 h.

9. The method for preparing optically active 2-fluoropropionate according to claim 1, characterized in that: The post-processing in step two includes filtration, washing, drying, concentration, and distillation. The target product, optically active 2-fluoropropionate, has a purity of ≥99%, a yield of ≥87%, and an ee value of ≥97%.

10. The method for preparing optically active 2-fluoropropionate according to claim 1, characterized in that: The chemical reaction formula for step two is:

Images