Preparation method of potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate

Abstract

The present invention provides a preparation method of (2-fluoro-6-hydroxyphenyl) potassium trifluoroborate. The preparation method comprises the following steps: (1) reacting 3-fluorophenol and chloromethyl ether to obtain a compound shown in Formula I; (2) in the presence of a lithium reagent, reacting the compound shown in Formula I obtained in step (1) with isopropyl alcohol pinacol borate to obtain a compound shown in Formula II; (3) in the presence of an acid, reacting the compound shown in Formula II obtained in step (2) with potassium fluoride to obtain (2-fluoro-6-hydroxyphenyl) potassium trifluoroborate. The preparation process of the present invention does not require the use of a hazardous reagent, boron tribromide, and the yield is also greatly improved, the process is simple, convenient to operate, and is easy to industrialize.

Description

Technical Field

[0001] The invention belongs to the field of pharmaceutical intermediate synthesis, and particularly relates to a preparation method of potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate. Background Art

[0002] Potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate is a pharmaceutical intermediate of traditional Chinese medicine. Its original synthesis route is as follows:

[0003]

[0004] The route starts from m-fluoroanisole, undergoes hydrogen extraction with butyl lithium, then adds trimethyl borate, demethylates it, and then prepares potassium trifluoroborate functional group.

[0005] However, the above-mentioned route involves the demethylation of boron trifluoride, which requires deep cooling. Boron trifluoride is also extremely volatile and corrosive, causing great harm to the human body. Furthermore, a corrosion-resistant Hastelloy kettle that can withstand deep cooling is also required, which greatly increases the cost of the entire route and makes the process more dangerous, restricting the industrial scale-up of this variety.

[0006] Therefore, it is urgent to develop a method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate which avoids the use of dangerous reagents such as boron tribromide, has a greatly improved yield, is simple in process, convenient to operate, and is easy to industrialize. Summary of the Invention

[0007] In view of the shortcomings of the prior art, the present invention aims to provide a method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate. The method avoids the use of hazardous reagents such as boron tribromide, significantly improves yield, and has a simple process, convenient operation, and is amenable to industrial production.

[0008] To achieve this object, the present invention adopts the following technical solutions:

[0009] The present invention provides a method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate, which comprises the following steps:

[0010] (1) 3-Fluorophenol and chloromethyl ether are reacted to obtain a compound represented by Formula I, as shown in the following reaction formula:

[0011]

[0012] (2) In the presence of a lithium reagent, the compound of formula I obtained in step (1) is reacted with isopropyl pinacol borate to obtain a compound of formula II. The reaction formula is as follows:

[0013]

[0014] (3) In the presence of an acid, the compound represented by formula II obtained in step (2) is reacted with potassium fluoride to obtain potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate. The reaction formula is shown below:

[0015]

[0016] In the present invention, the preparation method starts from m-fluorophenol, which is cheaper than m-fluoroanisole, and is completed in three steps: hydroxyl protection, hydroboration with a lithium reagent at low temperature, and then removal of hydroxyl protection while preparing potassium trifluoroborate functional group. The route avoids the use of dangerous reagent boron tribromide, and the yield is greatly improved. The process is simple, easy to operate, and easy to industrialize.

[0017] Preferably, in step (1), the molar ratio of 3-fluorophenol to chloromethyl ether is 1:(1-1.2), for example, 1:1, 1:1.05, 1:1.1, 1:1.15, 1:1.2, etc.

[0018] Preferably, in step (1), the reaction is carried out in the presence of a base, and the molar ratio of 3-fluorophenol to the base is 1:(1-2), for example, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, etc.

[0019] Preferably, the base comprises any one of potassium carbonate, cesium carbonate, sodium carbonate, sodium bicarbonate or potassium bicarbonate, or a combination of at least two thereof, preferably potassium carbonate.

[0020] Preferably, in step (1), the reaction is carried out in a solvent.

[0021] Preferably, the solvent includes any one of acetonitrile, tetrahydrofuran, dichloroethane, N,N-dimethylformamide, N,N-dimethylacetamide, isopropyl ether or methyl tert-butyl ether, or a combination of at least two thereof, preferably acetonitrile.

[0022] Preferably, in step (1), the reaction temperature is 20-60°C, for example, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 55°C, etc., and the reaction time is 6-24h, for example, 6h, 8h, 10h, 12h, 14h, 16h, 18h, 20h, 22h, 24h, etc.

[0023] Preferably, in step (1), the specific steps of the reaction are: after mixing 3-fluorophenol and a base in a solvent, adding chloromethyl ether dropwise under stirring at 20-30°C (for example, 20°C, 22°C, 24°C, 26°C, 28°C, 30°C, etc.), heating the system to 45-55°C (for example, 45°C, 47°C, 49°C, 51°C, 53°C, 55°C, etc.) after the addition is completed, and keeping the reaction warm for 8-14h (for example, 8h, 9h, 10h, 11h, 12h, 13h, 14h, etc.).

[0024] Preferably, in step (1), the post-treatment after the reaction is: filtering the reaction solution and concentrating the filtrate.

[0025] Preferably, in step (2), the molar ratio of the compound represented by formula I, isopropyl pinacol borate and lithium reagent is 1:(1-1.2):(1-1.2), for example, it can be 1:1:1, 1:1:1.05, 1:1.05:1.05, 1:1.05:1.1, 1:1.1:1.1, 1:1.1:1.15, 1:1.15:1.15, 1:1.2:1.2, etc.

[0026] Preferably, the lithium reagent includes any one of n-butyllithium, sec-butyllithium, lithium diisopropylamide or lithium tetramethylethylenediamine, or a combination of at least two thereof, preferably lithium diisopropylamide.

[0027] Preferably, in step (2), the reaction is carried out in a solvent.

[0028] Preferably, the solvent comprises any one of acetonitrile, tetrahydrofuran or diethyl ether or a combination of at least two thereof, preferably tetrahydrofuran.

[0029] Preferably, in step (2), the reaction temperature is -80 to -60°C, for example, -80°C, -75°C, -70°C, -65°C, -60°C, etc., and the reaction time is 3-5h, for example, 3h, 3.2h, 3.4h, 3.6h, 3.8h, 4h, 4.2h, 4.4h, 4.6h, 4.8h, 5h, etc.

[0030] Preferably, in step (2), the specific steps of the reaction are: dissolving the compound represented by formula I in a solvent, cooling to -80 to -60°C (for example, -80°C, -75°C, -70°C, -65°C, -60°C, etc.), adding lithium diisopropylamide dropwise under stirring, and after the addition is complete, keeping the system at -80 to -60°C (for example, -80°C, -75°C, -70°C, -65°C, -60°C, etc.) and stirring for 40-50 minutes (for example, 40 minutes). in, 42 min, 44 min, 46 min, 48 min, 50 min, etc.); then, isopropyl pinacol borate is added dropwise under stirring. After the addition is completed, the system is kept warm at -80 to -60 ° C (for example, -80 ° C, -75 ° C, -70 ° C, -65 ° C, -60 ° C, etc.) and stirred for 2-4 h (for example, 2 h, 2.2 h, 2.4 h, 2.6 h, 2.8 h, 3 h, 3.2 h, 3.4 h, 3.6 h, 3.8 h, 4 h, etc.).

[0031] Preferably, in step (2), the post-reaction post-treatment is as follows: adding citric acid aqueous solution to the reaction solution for quenching, adding water for separation, extracting the aqueous layer with methyl tert-butyl ether, and combining the organic phases; drying, filtering, and concentrating the organic phases in sequence; dissolving the concentrated product in a mixture of methanol and water, adding n-heptane, and stirring, standing, and separating the mixture in sequence; and drying, filtering, and concentrating the organic phases in sequence to obtain the compound represented by Formula II.

[0032] Preferably, the concentration of the citric acid aqueous solution is 0.1-1M, for example, 0.1M, 0.2M, 0.4M, 0.6M, 0.8M, 1M, etc., preferably 0.5M.

[0033] Preferably, the volume ratio of methanol to water is (1-3):1, for example, 1:1, 1.2:1, 1.4:1, 1.6:1, 1.8:1, 2:1, 2.2:1, 2.4:1, 2.6:1, 2.8:1, 3:1, etc., preferably 2:1;

[0034] Preferably, the volume ratio of n-heptane to the mixture of methanol and water is (0.5-2):1, for example, it can be 0.5:1, 0.6:1, 0.8:1, 1:1, 1.2:1, 1.4:1, 1.6:1, 1.8:1, 2:1, etc., preferably 1:1.

[0035] Preferably, in step (3), the molar ratio of the compound represented by formula II, potassium fluoride and acid is 1:(3-5):(2-3), for example, it can be 1:3:2, 1:3:2.5, 1:3:3, 1:3.5:2, 1:3.5:2.5, 1:3.5:3, 1:4:2, 1:4:2.5, 1:4:3, 1:5:2, 1:5:2.5, 1:5:3, etc.

[0036] Preferably, the acid comprises any one of formic acid, acetic acid or citric acid or a combination of at least two thereof, preferably citric acid.

[0037] Preferably, in step (3), the reaction is carried out in a solvent.

[0038] Preferably, the solvent comprises any one or a combination of at least two of acetonitrile, tetrahydrofuran, 1,4-dioxane or water, preferably a combination of tetrahydrofuran and water.

[0039] Preferably, in step (3), the reaction temperature is 20-30°C, for example, 20°C, 22°C, 24°C, 26°C, 28°C, 30°C, etc., and the reaction time is 6-24h, for example, 6h, 8h, 10h, 12h, 14h, 16h, 18h, 20h, 22h, 24h, etc.

[0040] Preferably, in step (3), the specific steps of the reaction are: dissolving the compound represented by formula II and potassium fluoride in an aqueous solvent, adding acid in batches and replenishing solvent, and reacting at 20-30°C (for example, 20°C, 22°C, 24°C, 26°C, 28°C, 30°C, etc.) for 6-24h, for example, 6h, 8h, 10h, 12h, 14h, 16h, 18h, 20h, 22h, 24h, etc.

[0041] Preferably, in step (3), the post-reaction post-treatment is as follows: filtering the reaction solution, taking the filter cake, placing it in isopropanol for slurrying, filtering, taking the filter cake and dissolving it in ethyl acetate, filtering, taking the filtrate and concentrating it, and drying it to obtain potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate.

[0042] Compared with the prior art, the present invention has the following beneficial effects:

[0043] (1) The present invention starts from m-fluorophenol, which is cheaper than m-fluoroanisole, and is prepared by hydroxyl protection, low-temperature hydroboration, and then removing the hydroxyl protection in three steps while preparing the potassium trifluoroborate functional group. The process bypasses the dangerous reagent boron tribromide, and the yield is greatly improved. The process is simple, easy to operate, and easy to industrialize.

[0044] (2) The total yield of the three steps of the synthetic route of the present invention is above 84%, and the purity of the prepared potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate is above 99%. DETAILED DESCRIPTION

[0045] The technical solution of the present invention is further described below by way of specific embodiments. It should be understood by those skilled in the art that the embodiments are merely to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0046] Example 1

[0047] This embodiment provides a method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate, which comprises the following steps:

[0048] The synthetic route is:

[0049]

[0050] (1) 400 g (3.57 mol) of 3-fluorophenol was dissolved in 3.5 L of acetonitrile, potassium carbonate (739 g, 5.35 mol) was added, and the mixture was stirred at 25°C. Chloromethyl ether (371 g, 3.92 mol) was added dropwise. The temperature was slowly raised to 50°C, stirred at this temperature for 12 h, filtered, and concentrated at 40°C to obtain 607 g of a colorless oily liquid with a yield of 100% and a purity of 98%.

[0051] 1 H NMR (CDCl3 / 400MHz)1.11(t,3H),3.42(q,2H),5.16(s,2H),6.71(m,1H),6.74-6.82(m,2H),7.21(m,1H);

[0052] (2) The compound of formula I (420 g, 2.47 mol) was dissolved in tetrahydrofuran (6 L), cooled to -70 ° C, and stirred. Diisopropylamine lithium (2.72 L, 1 M, 2.72 mol) was added dropwise. After the addition was completed, stirring was continued at -70 ° C for 45 min. Then, isopropyl alcohol pinacol borate (528 g, 2.84 mol) was added dropwise. Stirring was continued at -70 ° C for 3 h. 0.5 M citric acid aqueous solution 300 mL was added dropwise to quench the mixture. Then the temperature was raised to 25°C, 2 L of water was added, the liquid was separated, the aqueous layer was extracted twice with 300 mL of methyl tert-butyl ether, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated at 40°C. The residue was dissolved in 2 L of a mixture of methanol and water (volume ratio of 2:1), and then n-heptane (2 L) was added. The mixture was stirred at 25°C for 1 h, allowed to stand, the liquid was separated, the upper organic phase was dried, filtered, and concentrated at 40°C to obtain 694 g of a colorless oily liquid with a yield of 95% and a purity of 95%;

[0053] 1 H NMR (CDCl3, 400M) δ: 1.11 (t, 3H), 1.26 (s, 12H), 3.26 (q, 2H), 5.03 (s, 2H), 6.68 (m, 1H), 6.70-6.75 (m, 2H), 7.16 (m, 1H);

[0054] (3) The compound represented by Formula II (300 g, 1.01 mol) was dissolved in 2 L of tetrahydrofuran and stirred to dissolve. Potassium fluoride (235 g, 4.05 mol) and 350 mL of water were added to the reactor, and citric acid (480 g, 2.5 mol) was added in three batches. Then, 300 mL of water and 700 mL of tetrahydrofuran were added. The mixture was stirred at 25°C for 12 h, filtered, and the filter cake was slurried with isopropanol and filtered. The filter cake was redissolved in 5 times the volume of ethyl acetate, and the insoluble matter was filtered off. The mixture was concentrated at 30°C and dried to obtain 194 g of an off-white powder with a yield of 88% and a purity of 99%.

[0055] 1 H NMR (CDCl3 / 400MHz): 6.50-6.61 (m, 1H), 6.83 (q, 1H), 8.10 (q, 1H).

[0056] Example 2

[0057] This embodiment provides a method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate, which comprises the following steps:

[0058] The synthetic route is:

[0059]

[0060] (1) 300 g (2.67 mol) of 3-fluorophenol was dissolved in 4 L of tetrahydrofuran, cesium carbonate (1.3 g, 4.0 mol) was added, and the mixture was stirred at 25°C. Chloromethyl ether (279 g, 2.94 mol) was added dropwise. The temperature was slowly raised to 55°C, stirred at this temperature for 10 h, filtered, and concentrated at 35°C to obtain 455 g of a colorless oily liquid with a yield of 100% and a purity of 98%.

[0061] 1 H NMR (CDCl3 / 400MHz)1.11(t,3H),3.42(q,2H),5.16(s,2H),6.71(m,1H),6.74-6.82(m,2H),7.21(m,1H);

[0062] (2) The compound of formula I (400 g, 2.35 mol) was dissolved in tetrahydrofuran (6 L), cooled to -75 ° C, and stirred. Diisopropylamine lithium (2.58 L, 1 M, 2.58 mol) was added dropwise. After the addition, stirring was continued at -75 ° C for 40 min. Then, isopropyl alcohol pinacol borate (502 g, 2.70 mol) was added dropwise. Stirring was continued at -75 ° C for 2.5 h. 0.5 M citric acid aqueous solution 300 mL was added dropwise to quench the mixture. The mixture was naturally stirred. The temperature was raised to 20°C, 1.5 L of water was added, the liquid was separated, the aqueous layer was extracted three times with 200 mL of methyl tert-butyl ether, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated at 40°C. The residue was dissolved in 2 L of a mixture of methanol and water (volume ratio of 2:1), and then n-heptane (2 L) was added. The mixture was stirred at 25°C for 40 min, allowed to stand, the liquid was separated, the upper organic phase was dried, filtered, and concentrated at 40°C to obtain 662 g of a colorless oily liquid with a yield of 95% and a purity of 96%.

[0063] 1 H NMR (CDCl3, 400M) δ: 1.11 (t, 3H), 1.26 (s, 12H), 3.26 (q, 2H), 5.03 (s, 2H), 6.68 (m, 1H), 6.70-6.75 (m, 2H), 7.16 (m, 1H);

[0064] (3) The compound represented by Formula II (500 g, 1.69 mol) was dissolved in 3.5 L of tetrahydrofuran and stirred to dissolve. Potassium fluoride (392 g, 6.76 mol) and 500 mL of water were added to the reactor, and citric acid (810 g, 4.22 mol) was added in four batches. Then, 400 mL of water and 800 mL of tetrahydrofuran were added, and the mixture was stirred at 30°C for 10 h. The mixture was filtered and the filter cake was slurried with isopropanol and filtered. The filter cake was redissolved in 5 times the volume of ethyl acetate, and the insoluble matter was filtered off. The mixture was concentrated at 30°C and dried to obtain 332 g of an off-white powder with a yield of 90% and a purity of 99%.

[0065] 1 H NMR (CDCl3 / 400MHz): 6.50-6.61 (m, 1H), 6.83 (q, 1H), 8.10 (q, 1H).

[0066] Example 3

[0067] This embodiment provides a method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate, which comprises the following steps:

[0068] The synthetic route is:

[0069]

[0070] (1) 400 g (3.57 mol) of 3-fluorophenol was dissolved in 3.5 L of dichloroethane, potassium carbonate (739 g, 5.35 mol) was added, and the mixture was stirred at 30°C. Chloromethyl ether (371 g, 3.92 mol) was added dropwise. The temperature was slowly raised to 45°C, stirred at this temperature for 14 h, filtered, and concentrated at 40°C to obtain 608 g of a colorless oily liquid with a yield of 100% and a purity of 99%.

[0071] 1 H NMR (CDCl3 / 400MHz)1.11(t,3H),3.42(q,2H),5.16(s,2H),6.71(m,1H),6.74-6.82(m,2H),7.21(m,1H);

[0072] (2) The compound of formula I (420 g, 2.47 mol) was dissolved in tetrahydrofuran (6 L), cooled to -65 ° C, and lithium diisopropylamide (2.72 L, 1 M, 2.72 mol) was added dropwise with stirring. After the addition, stirring was continued at -65 ° C for 50 min, and then isopropyl alcohol pinacol borate (528 g, 2.84 mol) was added dropwise, and stirring was continued at -65 ° C for 3.5 h; 0.5 M citric acid aqueous solution 300 mL was added dropwise to quench the mixture. The temperature was naturally raised to 25°C, 2 L of water was added, the liquid was separated, the aqueous layer was extracted three times with 300 mL of methyl tert-butyl ether, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated at 35°C. The residue was dissolved in 2 L of a mixture of methanol and water (volume ratio of 2:1), and then n-heptane (2 L) was added. The mixture was stirred at 20°C for 2 h, allowed to stand, the liquid was separated, the upper organic phase was dried, filtered, and concentrated at 35°C to obtain 705 g of a colorless oily liquid with a yield of 96% and a purity of 94%.

[0073] 1 H NMR (CDCl3, 400M) δ: 1.11 (t, 3H), 1.26 (s, 12H), 3.26 (q, 2H), 5.03 (s, 2H), 6.68 (m, 1H), 6.70-6.75 (m, 2H), 7.16 (m, 1H);

[0074] (3) The compound represented by Formula II (300 g, 1.01 mol) was dissolved in 2 L of tetrahydrofuran and stirred to dissolve. Potassium fluoride (235 g, 4.05 mol) and 350 mL of water were added to the reactor, and citric acid (480 g, 2.5 mol) was added in two batches. Then, 300 mL of water and 700 mL of tetrahydrofuran were added. The mixture was stirred at 20°C for 14 h, filtered, and the filter cake was slurried with isopropanol and filtered. The filter cake was redissolved in 5 times the volume of ethyl acetate, and the insoluble matter was filtered off. The mixture was concentrated at 30°C and dried to obtain 194 g of an off-white powder with a yield of 88% and a purity of 98%.

[0075] 1 H NMR (CDCl3 / 400MHz): 6.50-6.61 (m, 1H), 6.83 (q, 1H), 8.10 (q, 1H).

[0076] Comparative Example 1

[0077] This comparative example provides a preparation method of potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate, which comprises the following steps:

[0078] The synthetic route is:

[0079]

[0080] (1) 79 g of diisopropylamine was added to a 2000 mL three-necked flask, and 400 mL of tetrahydrofuran was added. The mixture was cooled to -30 ° C., 228 g of n-butyl lithium was added dropwise, and the mixture was stirred for 30 min. The mixture was cooled to -70 ° C. A mixed solution of 70 g of 3-fluoroanisole and 400 mL of tetrahydrofuran was added dropwise, and the mixture was stirred for 30 min. 162 g of triethyl borate was added dropwise, and the temperature was controlled not to exceed -70 ° C. After the mixture was stirred for 1 h, 2 M hydrochloric acid was added dropwise to acidify the mixture, and methyl tert-butyl ether was extracted three times. The organic phases were combined, concentrated to half the volume, and n-heptane was added. The mixture was stirred at 5 ° C for 3 h. The filter cake was washed with n-heptane and dried to obtain 2-fluoro-6-methoxyphenylboronic acid with a yield of about 75% and a purity of 93%.

[0081] (2) 75 g of 2-fluoro-6-methoxyphenylboronic acid was dissolved in 400 mL of dichloromethane, cooled to -35°C, and 170 g of boron tribromide was slowly pumped in under vacuum, the temperature was controlled below -30°C, and the reaction was kept warm for 2 h. After the addition was completed, the mixture was quenched with ice water; 1 L of methyl tert-butyl ether was added and continued to stir for 2 h. The liquid was separated, and the aqueous phase was extracted twice with methyl tert-butyl ether. The organic phases were combined and concentrated to about 100 mL. 1 L of n-heptane was added and stirred for 2 h. Then, the mixture was filtered and dried at 30°C to obtain 2-fluoro-6-hydroxyphenylboronic acid with a yield of 80% and a purity of 92%.

[0082] (3) 1100 mL of acetonitrile was added to a 2000 mL reaction flask, 43 g of 2-fluoro-6-hydroxyphenylboronic acid was added, and the mixture was stirred to dissolve. 70.5 g of potassium fluoride and 108 g of water were added, and a mixed solution of tartaric acid (114 g of tartaric acid dissolved in 540 mL of tetrahydrofuran and 90 g of water) was added dropwise, and the mixture was stirred for 2 h. The mixture was filtered, and the filter cake was washed with tetrahydrofuran. The reaction mixture was concentrated at 30° C. until a large amount of solid precipitated. 100 mL of isopropanol was added, and the mixture was stirred for 1 h. The mixture was filtered, and the solid was washed with isopropanol to obtain potassium 2-fluoro-hydroxyphenyl trifluoroborate with a yield of 75% and a purity of 95%.

[0083] The applicant declares that the present invention illustrates the preparation method of potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate of the present invention through the above-mentioned embodiment, but the present invention is not limited to the above-mentioned embodiment, that is, it does not mean that the present invention must rely on the above-mentioned embodiment to be implemented. It should be clear to those skilled in the art that any improvement of the present invention, equivalent replacement of various raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the scope of protection and disclosure of the present invention.

Claims

1. A method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate, characterized in that: The preparation method comprises the following steps: (1) 3-Fluorophenol and chloromethyl ether are reacted to obtain a compound represented by Formula I, as shown in the following reaction formula: (2) In the presence of a lithium reagent, the compound of formula I obtained in step (1) is reacted with isopropyl pinacol borate to obtain a compound of formula II, as shown in the following reaction formula: (3) In the presence of an acid, the compound represented by formula II obtained in step (2) is reacted with potassium fluoride to obtain potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate. The reaction formula is shown below: In step (1), the reaction temperature is 45-55° C. and the reaction time is 8-14 h; In step (2), the reaction temperature is -80 to -60°C, and the reaction time is 3 to 5 hours.

2. The preparation method of potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 1, wherein In step (1), the molar ratio of 3-fluorophenol to chloromethyl ether is 1:(1-1.2).

3. The preparation method of potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 1, wherein In step (1), the reaction is carried out in the presence of a base, and the molar ratio of the 3-fluorophenol to the base is 1:(1-2).

4. The preparation method of potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 3, wherein The base includes any one of potassium carbonate, cesium carbonate, sodium carbonate, sodium bicarbonate or potassium bicarbonate, or a combination of at least two thereof.

5. The preparation method of potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 4, wherein The base is potassium carbonate.

6. The preparation method of potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 1, wherein In step (1), the reaction is carried out in a solvent.

7. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 6, wherein The solvent includes any one of acetonitrile, tetrahydrofuran, dichloroethane, N,N-dimethylformamide, N,N-dimethylacetamide, isopropyl ether or methyl tert-butyl ether, or a combination of at least two thereof.

8. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 7, wherein The solvent is acetonitrile.

9. The preparation method of potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 1, characterized in that In step (1), the specific steps of the reaction are: after mixing 3-fluorophenol and a base in a solvent, adding chloromethyl ether dropwise at 20-30° C. under stirring, heating the system to 45-55° C. after the addition is completed, and keeping the temperature for reaction for 8-14 hours.

10. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 1, wherein In step (1), the post-reaction post-treatment is as follows: filtering the reaction solution and concentrating the filtrate.

11. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 1, wherein In step (2), the molar ratio of the compound represented by formula I, isopropyl pinacol borate and lithium reagent is 1:(1-1.2):(1-1.2).

12. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 1, wherein The lithium reagent includes any one of n-butyl lithium, sec-butyl lithium, lithium diisopropylamide or lithium tetramethylethylenediamine, or a combination of at least two thereof.

13. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 12, wherein The lithium reagent is lithium diisopropylamide.

14. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 1, wherein In step (2), the reaction is carried out in a solvent.

15. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 14, wherein The solvent includes any one of acetonitrile, tetrahydrofuran or diethyl ether, or a combination of at least two of them.

16. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 15, wherein The solvent is tetrahydrofuran.

17. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 1, wherein In step (2), the specific steps of the reaction are: dissolving the compound represented by formula I in a solvent, cooling to -80 to -60°C, adding lithium diisopropylamide dropwise with stirring, and keeping the system at -80 to -60°C with stirring for 40-50 minutes after the addition is complete; then adding isopropyl alcohol pinacol borate dropwise with stirring, and keeping the system at -80 to -60°C with stirring for 2-4 hours after the addition is complete.

18. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 1, wherein In step (2), the post-reaction post-treatment is as follows: adding citric acid aqueous solution to the reaction solution for quenching, adding water for separation, extracting the aqueous layer with methyl tert-butyl ether, and combining the organic phases; drying, filtering, and concentrating the organic phases in sequence; dissolving the concentrated product in a mixture of methanol and water, adding n-heptane, and stirring, standing, and separating the mixture in sequence; and drying, filtering, and concentrating the organic phases in sequence to obtain the compound shown in Formula II.

19. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 18, wherein The concentration of the citric acid aqueous solution is 0.1-1M.

20. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 19, wherein The concentration of the citric acid aqueous solution is 0.5M.

21. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 18, wherein The volume ratio of the methanol to water is (1-3):

1.

22. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 21, wherein The volume ratio of the methanol to water is 2:

1.

23. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 18, wherein The volume ratio of the n-heptane to the mixed solution of methanol and water is (0.5-2):

1.

24. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 23, wherein The volume ratio of the n-heptane to the mixed liquid of methanol and water is 1:

1.

25. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 1, wherein In step (3), the molar ratio of the compound represented by formula II, potassium fluoride and acid is 1:(3-5):(2-3).

26. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 1, wherein The acid includes any one of formic acid, acetic acid or citric acid, or a combination of at least two of them.

27. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 26, wherein The acid is citric acid.

28. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 1, wherein In step (3), the reaction is carried out in a solvent.

29. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 28, wherein The solvent includes any one of acetonitrile, tetrahydrofuran, 1,4-dioxane or water, or a combination of at least two thereof.

30. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 29, wherein The solvent is a combination of tetrahydrofuran and water.

31. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 1, wherein In step (3), the reaction temperature is 20-30° C., and the reaction time is 6-24 h.

32. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 1, wherein In step (3), the specific steps of the reaction are: dissolving the compound represented by formula II and potassium fluoride in an aqueous solvent, adding acid in batches and replenishing solvent, and reacting at 20-30° C. for 6-24 hours.

33. The method for preparing potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate according to claim 1, wherein In step (3), the post-reaction post-treatment is as follows: filtering the reaction solution, taking the filter cake, placing it in isopropanol for slurrying, filtering, taking the filter cake and dissolving it in ethyl acetate, filtering, taking the filtrate and concentrating it, and drying it to obtain potassium (2-fluoro-6-hydroxyphenyl) trifluoroborate.

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