Production method of diethyl (3-pyridyl)-borane as well as obtained product and detection method of diethyl (3-pyridyl)-borane

Abstract

The invention discloses a production method of diethyl (3-pyridyl)-borane and a product obtained by the production method. The production method is mild in reaction condition and convenient to operate and control, and the obtained product is high in yield, high in purity, low in energy consumption, low in cost and suitable for industrial production. Besides, the invention also provides a high performance liquid chromatography detection method of diethyl (3-pyridyl)-borane, the detected chromatographic peaks have no obvious interference, the separation degree is high, the detection result is accurate and reliable, the relevant regulations and / or requirements of accuracy and precision are met, and qualitative and / or quantitative detection can be realized. Therefore, the method has very important economic and social values.

Description

Technical Field

[0001] The invention belongs to the field of borane products, and particularly relates to a production method of diethyl (3-pyridyl)-borane suitable for industrialization, a product obtained therefrom and a detection method. Background Art

[0002] Organoboranes are an important class of organic intermediates that can undergo Suzuki reactions to break carbon-boron bonds and generate a series of compounds such as hydrocarbons, ethers, and ketones. They are very important in the synthesis of chemical products and are also widely used in drug synthesis.

[0003] Among them, diethyl (3-pyridyl)-borane (CAS No.: 89878-14-8) is an important borane product that can be used to prepare drugs such as ivabradine, abiraterone or their salts (see: CN 113372274 A, CN103172690 A, etc.).

[0004] However, most of the existing technical synthesis methods of diethyl (3-pyridyl) -borane remain at the laboratory stage. For example, the synthesis method of diethyl (3-pyridyl) -borane disclosed by Zhang Jing et al. (Zhang Jing, Jin Fengmin. Synthesis of diethyl (3-pyridyl) -borane [J]. Chemical Industry and Engineering, 2013, 30 (3): 4) has an immature process route and / or conditions, and its output is only a few grams or tens of grams, which cannot meet the actual needs of the industry and / or the market, and seriously affects and restricts the supply chain security of diethyl (3-pyridyl) -borane and its downstream industries.

[0005] In view of this, the present invention is proposed. Summary of the Invention

[0006] In response to the problems and / or deficiencies of the prior art, one of the objectives of the present invention is to provide a method for producing diethyl(3-pyridyl)borane. This method has mild reaction conditions, is easy to operate and control, and produces a high yield, high purity, low energy consumption, low cost, and is suitable for industrial production. Furthermore, a high-performance liquid chromatography method for detecting diethyl(3-pyridyl)borane is provided, which exhibits no significant interference between detected chromatographic peaks, high resolution, and accurate and reliable detection results that meet relevant regulations and / or requirements for accuracy and precision, enabling qualitative and / or quantitative detection.

[0007] The present invention provides a method for producing diethyl (3-pyridyl) -borane, comprising the following steps: with or without protection by an inert gas (including but not limited to argon, helium, nitrogen, etc.), in the presence of ethyl magnesium bromide and ethyl bromide, reacting magnesium, 2-chloropropane and 3-bromopyridine in an ether solvent at 10° C. to 40° C. for 10 to 30 hours, then adding diethyl methoxy borane or a solution thereof in an ether solvent and reacting at 0° C. to 10° C. for 5 to 15 hours to generate diethyl (3-pyridyl) -borane; wherein magnesium, 2-chloropropane, The amount of the solution of 3-bromopyridine, diethylmethoxyborane or its ether solvent is greater than or equal to 1 kg; preferably, the amount of magnesium, 2-chloropropane, 3-bromopyridine, diethylmethoxyborane or its ether solvent is in the range of 1 kg to 500 kg (for example: 1 kg, 5 kg, 10 kg, 20 kg, 30 kg, 40 kg, 50 kg, 60 kg, 70 kg, 80 kg, 90 kg, 100 kg, 120 kg, 150 kg, 200 kg, 250 kg, 300 kg, 400 kg, etc.).

[0008] Further,

[0009] In any of the above technical solutions (production method of diethyl (3-pyridyl) -borane), the amounts of ethylmagnesium bromide and ethyl bromide used per mole of 3-bromopyridine are 0.02 mol to 0.2 mol (for example: 0.02 mol, 0.03 mol, 0.04 mol, 0.05 mol, 0.06 mol, 0.07 mol, 0.08 mol, 0.09 mol, 0.10 mol, 0.11 mol, 0.12 mol, 0.13 mol, 0.14 mol, 0.15 mol, 0.16 mol, 0.17 mol, 0.18 mol, 0.19 mol, 0.2 mol, etc.), 0 0.02mol~0.2mol (for example: 0.02mol, 0.03mol, 0.04mol, 0.05mol, 0.06mol, 0.07mol, 0.08mol, 0.09mol, 0.10mol, 0.11mol, 0.12mol, 0.13mol, 0.14mol, 0.15mol, 0.16mol, 0.17mol, 0.18mol, 0.19mol, 0.2mol, etc.); preferably, the amount of ethylmagnesium bromide and ethyl bromide per mole of 3-bromopyridine is 0.03mol~0.1mol, 0.05mol~0.1mol, respectively;

[0010] And / or, the amount of magnesium and 2-chloropropane used per mole of 3-bromopyridine is 1 mol to 1.5 mol (for example, 1.0 mol, 1.1 mol, 1.2 mol, 1.3 mol, 1.4 mol, 1.5 mol, etc.), 1 mol to 1.5 mol (for example, 1.0 mol, 1.1 mol, 1.2 mol, 1.3 mol, 1.4 mol, 1.5 mol, etc.); preferably, the amount of magnesium and 2-chloropropane used per mole of 3-bromopyridine is 1.15 mol to 1.35 mol, 1.05 mol to 1.25 mol, respectively;

[0011] And / or, the amount of diethylmethoxyborane used per mole of 3-bromopyridine is 1 mol to 1.5 mol (for example, 1.0 mol, 1.1 mol, 1.2 mol, 1.3 mol, 1.4 mol, 1.5 mol, etc.); preferably, the amount of diethylmethoxyborane used per mole of 3-bromopyridine is 1 mol to 1.25 mol;

[0012] And / or, the amount of the ether solvent corresponding to each mole of 3-bromopyridine is 0.2 kg to 2 kg (for example, 0.2 kg, 0.3 kg, 0.4 kg, 0.5 kg, 0.6 kg, 0.7 kg, 0.8 kg, 0.9 kg, 1.0 kg, 1.5 kg, etc.); preferably, the amount of the ether solvent corresponding to each mole of 3-bromopyridine is 0.4 kg to 1 kg.

[0013] Further,

[0014] In any of the above technical solutions (method for producing diethyl(3-pyridyl)borane), the inert gas is nitrogen or argon; and / or the ether solvent is tetrahydrofuran; and / or the solution of diethylmethoxyborane in an ether solvent is a solution of diethylmethoxyborane in tetrahydrofuran.

[0015] Further,

[0016] In any of the above technical solutions (method for producing diethyl(3-pyridyl)-borane), the reaction step of magnesium, 2-chloropropane and 3-bromopyridine in an ether solvent is as follows: magnesium and 2-chloropropane are reacted at 25°C to 35°C for 5 to 20 hours, and then 3-bromopyridine is added and reacted at 20°C to 30°C for 5 to 10 hours;

[0017] and / or, the reaction temperature of adding the solution of diethylmethoxyborane or its ether solvent is 0° C. to 5° C.; and / or, the reaction time of adding the solution of diethylmethoxyborane or its ether solvent is 7.5 hours to 15 hours.

[0018] Further,

[0019] Any of the above technical solutions (methods for producing diethyl (3-pyridyl) -borane) further includes a post-treatment step of adding hydrochloric acid to quench the reaction, allowing the mixture to stand, separating the liquids, taking the organic phase, drying it without drying or adding anhydrous sodium sulfate, distilling it under reduced pressure until no fraction is produced, adding isopropanol, stirring and maintaining the temperature at 60° C. to 70° C., then cooling it to 5° C., precipitating a solid, centrifuging or filtering it, and drying it to obtain diethyl (3-pyridyl) -borane;

[0020] Preferably, the concentration of the hydrochloric acid is 12 wt% to 38 wt% (for example, 15 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, etc.).

[0021] The present invention also provides a diethyl (3-pyridyl) -borane product, which is prepared by any of the above production methods, and the HPLC purity of the diethyl (3-pyridyl) -borane is ≥99.0%.

[0022] The present invention also provides a high performance liquid chromatography (HPLC) method for detecting diethyl (3-pyridyl)-borane products. The chromatographic conditions of the HPLC method include:

[0023] Chromatographic column: C18 column or its equivalent;

[0024] Mobile phase A: water; mobile phase B: acetonitrile;

[0025] Perform gradient elution according to the following program:

[0026] Time / min Mobile phase A / %, volume percentage Mobile phase B / %, volume percentage 0 55 45 5 55 45 25 5 95 55 5 95 60 55 45 70 55 45

[0027] Alternatively, perform a gradient elution as follows:

[0028]

[0029]

[0030] Detection wavelength: 180-280 nm (for example: 185 nm, 190 nm, 195 nm, 200 nm, 205 nm, 210 nm, 215 nm, 220 nm, 225 nm, 230 nm, 235 nm, 238 nm, 240 nm, 242 nm, 245 nm, 250 nm, 255 nm, 260 nm, 265 nm, 270 nm, 275 nm, etc.); preferably, the detection wavelength is 205 nm or 268 nm.

[0031] Further,

[0032] In any of the above technical solutions (high performance liquid chromatography detection method), the chromatographic column is a Kinetex C18 chromatographic column; and / or the specifications of the chromatographic column are: 4.6 mm×150 mm, 5 μm.

[0033] Further,

[0034] In any of the above technical solutions (high performance liquid chromatography detection method),

[0035] Column temperature: 15°C to 45°C (for example, 20°C, 25°C, 28°C, 30°C, 32°C, 35°C, 40°C, 42°C, 45°C, etc.); preferably, the column temperature is 40°C to 45°C;

[0036] and / or, injection volume: 0.5 μl to 25 μl (for example, the injection volume is 1 μl, 2 μl, 3 μl, 4 μl, 5 μl, 6 μl, 7 μl, 8 μl, 9 μl, 10 μl, 15 μl, 20 μl, 25 μl, etc.); preferably, the injection volume is 10 μl;

[0037] And / or, flow rate: 0.1ml / min~2ml / min (for example: flow rate is 0.5ml / min, 0.6ml / min, 0.7ml / min, 0.8ml / min, 0.9ml / min, 1.0ml / min, 1.2ml / min, 1.5ml / min, etc.); preferably, the flow rate is 1.0ml / min~1.5ml / min.

[0038] Further,

[0039] In any of the above technical solutions (high performance liquid chromatography detection method), the high performance liquid chromatography detection method is qualitative detection or quantitative detection; preferably, the high performance liquid chromatography detection method performs quantitative detection according to the internal standard method, external standard method or peak area normalization method.

[0040] The beneficial effects of the present invention are mainly in the following aspects:

[0041] The production method of diethyl (3-pyridyl) -borane provided by the present invention has mild reaction conditions, good safety, easy operation and control, and the obtained diethyl (3-pyridyl) -borane product has high yield and high purity, low energy consumption, low cost, and is suitable for industrial production;

[0042] The production method of diethyl (3-pyridyl)-borane provided by the present invention can not only well guarantee the product quality of diethyl (3-pyridyl)-borane (HPLC purity ≥99.0%), but also ensure the monthly output of the product is above 500 kg, which can better meet the market demand of downstream enterprises at home and abroad.

[0043] also,

[0044] The present invention provides a high-performance liquid chromatography (HPLC) method for detecting diethyl (3-pyridyl)-borane products. The method has no obvious interference between the chromatographic peaks detected, has high separation, and provides accurate and reliable detection results. The method can meet relevant regulations and / or requirements for accuracy and precision, thereby achieving qualitative and / or quantitative detection. The method provides an effective method for detecting diethyl (3-pyridyl)-borane products, thereby enabling more effective monitoring and assurance of product quality, thereby better protecting the product quality and / or safety of downstream synthetic drugs, and has good economic and social value. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Figure 1 This is the HPLC chart of diethyl (3-pyridyl) -borane obtained in Example 1.

[0046] Figure 2 This is the HPLC chart of diethyl (3-pyridyl) -borane obtained in Example 2. DETAILED DESCRIPTION

[0047] The present invention will be clearly and completely described below with reference to specific embodiments. Those skilled in the art will understand that the embodiments described below are only some embodiments of the present invention, rather than all embodiments, and are only used to illustrate the present invention and should not be regarded as limiting the scope of protection of the present invention.

[0048] In the present invention, if the specific conditions are not specified, the conventional conditions or the conditions recommended by the manufacturer shall be followed. If the manufacturer of the reagents or instruments is not specified, they are all conventional products that can be purchased commercially.

[0049] Regarding the definitions of terms used in the present invention, unless otherwise stated, the initial definitions provided for the terms in this document apply to the terms throughout the text; for terms not specifically defined herein, the meanings that can be given to them by those skilled in the art should be given based on the disclosure content and / or context.

[0050] Example 1 Production of diethyl (3-pyridyl) -borane

[0051] Under argon protection, 280 kg of tetrahydrofuran, 20 kg (about 823 mol) of magnesium powder, 15 kg of ethylmagnesium bromide in tetrahydrofuran solution (concentration of 25 wt%; containing about 28 mol of ethylmagnesium bromide), 5 kg (about 45.9 mol) of bromoethane and 60 kg (about 764 mol) of 2-chloropropane were added to the reactor, and the mixture was stirred at 30 ° C for 15 h. Then, 110 kg (about 696 mol) of 3-bromopyridine was added, and the mixture was stirred at 25 ° C for 9 h. After that, 140 kg of diethylmethoxyborane in tetrahydrofuran solution (concentration of 50 wt%; containing about 700 mol of diethylmethoxyborane) was added. The reaction was stirred at 5°C for 12h, 80kg of concentrated hydrochloric acid (concentration of 37wt%) and 120kg of water were added (quenching the reaction), allowed to stand, separated, the organic phase was taken, the aqueous phase was extracted 3 times with ethyl acetate (50kg×3), the organic phases were combined, 50kg of anhydrous sodium sulfate was added and dried, filtered, the filtrate was heated to 65°C and distilled under reduced pressure (pressure ≤0.09MPa) until no distillate was produced, then 60kg of isopropanol was added, the mixture was stirred at 65°C for 1h, cooled to 5°C, a solid was precipitated, centrifuged or filtered, and dried to obtain diethyl (3-pyridyl) -borane as a white or off-white powder with a yield of 82.5% (based on 3-bromopyridine).

[0052] 1.1 The purity of the diethyl (3-pyridyl) - borane obtained above was tested by high performance liquid chromatography (HPLC), as shown in Table 1 below:

[0053] Table 1. HPLC conditions for purity determination of diethyl(3-pyridyl)-borane

[0054]

[0055]

[0056] Test solution: Weigh about 25 mg of the sample to be tested (diethyl(3-pyridyl)-borane) into a 25 ml volumetric flask, add 5 ml of tetrahydrofuran to dissolve it, then dilute to the scale with acetonitrile and shake well.

[0057] According to the aforementioned HPLC conditions for sample injection and detection (in compliance with the provisions and requirements for methodological validation in the 2020 edition of the Chinese Pharmacopoeia), the HPLC purity of diethyl (3-pyridyl) -borane was calculated to be 99.94% by peak area normalization method. Figure 1 As shown: the retention time of diethyl(3-pyridyl)-borane is 45.217 min.

[0058] 1.2 The following high performance liquid chromatography (HPLC) method was used to determine the residual content of 3-bromopyridine in the diethyl (3-pyridyl)-borane obtained above (in compliance with the provisions and requirements for methodological validation in the 2020 edition of the Chinese Pharmacopoeia: the retention time of 3-bromopyridine is 7.847 min), as shown in Table 2 below:

[0059] Table 2. HPLC conditions for the detection of 3-bromopyridine in diethyl(3-pyridyl)-borane

[0060]

[0061]

[0062] Example 2 Production of diethyl (3-pyridyl) -borane

[0063] Under argon protection, 15 kg of tetrahydrofuran, 1 kg (about 41 mol) of magnesium powder, 1 kg of tetrahydrofuran solution of ethylmagnesium bromide (concentration of 25 wt%; containing about 1.9 mol of ethylmagnesium bromide), 0.25 kg (about 2.3 mol) of bromoethane and 3 kg (about 38 mol) of 2-chloropropane were added to the reactor, and the mixture was stirred at 30 ° C for 8 h. Then, 5 kg (about 31.6 mol) of 3-bromopyridine was added, and the mixture was stirred at 25 ° C for 5 h. After that, 7 kg of tetrahydrofuran solution of diethylmethoxyborane (concentration of 50 wt%; containing about 1.9 mol of diethylmethoxyborane) was added. alkane 35mol), stirred at 5 ° C for 8h, added 4kg concentrated hydrochloric acid (concentration of 37wt%) and 6kg water, allowed to stand, separated, the organic phase was taken, the aqueous phase was extracted 3 times with ethyl acetate (2.5kg×3), the organic phases were combined, anhydrous sodium sulfate was added for drying, filtered, the filtrate was heated to 65 ° C and distilled under reduced pressure until no fraction was produced, then 3kg isopropanol was added, the mixture was stirred at 65 ° C for 1h, cooled to 5 ° C, centrifuged or filtered, and dried to obtain off-white diethyl (3-pyridyl) -borane, with a yield of ≥ 80% (based on 3-bromopyridine) and a HPLC purity of 99.90%. Figure 2 shown.

[0064] Example 3 Production of diethyl (3-pyridyl) -borane

[0065] Under argon protection, 100 kg of tetrahydrofuran, 7.1 kg (about 292 mol) of magnesium powder, 5.5 kg of ethylmagnesium bromide in tetrahydrofuran solution (concentration of 25 wt%; containing about 10 mol of ethylmagnesium bromide), 1.8 kg (about 16.5 mol) of bromoethane and 21.4 kg (about 272.5 mol) of 2-chloropropane were added to the reactor, and the mixture was stirred at 30 ° C for 12 h, and then 39 kg (about 246.8 mol) of 3-bromopyridine was added, and the mixture was stirred at 25 ° C for 9 h, and then 50 kg of diethylmethoxyborane in tetrahydrofuran solution (concentration of 50 wt%; containing about 2- The mixture was stirred at 5°C for 10 hours, and 30 kg of concentrated hydrochloric acid (concentration of 37 wt%) and 45 kg of water were added. The mixture was allowed to stand for separation. The organic phase was taken, and the aqueous phase was extracted three times with ethyl acetate (18 kg × 3). The organic phases were combined, dried over anhydrous sodium sulfate, and filtered. The filtrate was heated to 65°C and distilled under reduced pressure until no fraction was produced. Then 22 kg of isopropanol was added, and the mixture was stirred at 65°C for 1 hour. The mixture was cooled to 5°C, centrifuged or filtered, and dried to obtain an off-white diethyl (3-pyridyl) -borane with a yield of ≥80% (based on 3-bromopyridine) and a HPLC purity of ≥99.0%.

[0066] Example 4 Production of diethyl (3-pyridyl) -borane

[0067] Under argon protection, 100 kg of tetrahydrofuran, 7.1 kg (about 292 mol) of magnesium powder, 5.5 kg of ethylmagnesium bromide in tetrahydrofuran solution (concentration of 25 wt%; containing about 10 mol of ethylmagnesium bromide), 1.8 kg (about 16.5 mol) of bromoethane and 21.4 kg (about 272.5 mol) of 2-chloropropane were added to the reactor, and the mixture was stirred at 30 ° C for 12 h, and then 39 kg (about 246.8 mol) of 3-bromopyridine was added, and the mixture was stirred at 25 ° C for 9 h, and then 50 kg of diethylmethoxyborane in tetrahydrofuran solution (concentration of 50 wt% The product is prepared by stirring at 5°C for 10 hours, adding 74 kg of 15 wt% dilute hydrochloric acid, allowing to stand, separating the liquids, taking the organic phase, extracting the aqueous phase three times with ethyl acetate (18 kg × 3), combining the organic phases, adding anhydrous sodium sulfate to dry, filtering, heating the filtrate to 65°C and distilling under reduced pressure until no fraction is obtained, then adding 22 kg of isopropanol, stirring at 65°C for 1 hour, cooling to 5°C, centrifuging or filtering, and drying to obtain off-white diethyl (3-pyridyl) - borane, with a yield of ≥ 80% (based on 3-bromopyridine) and a HPLC purity of ≥ 99.0%.

[0068] After operational testing, the production process method of the present invention has mild reaction conditions, good safety, easy operation and control, and the obtained diethyl (3-pyridyl) -borane product has high yield and high purity, low energy consumption, low cost, and is suitable for industrial production. It can not only well guarantee the product quality of diethyl (3-pyridyl) -borane (HPLC purity ≥99.0%), but also ensure its monthly output of more than 500 kg (based on an estimated 100% operating rate, the annual production supply capacity can reach more than 5000 kg), which can better meet the raw material supply capacity needs of downstream enterprises, thereby providing reliable protection for the supply chain security of diethyl (3-pyridyl) -borane related industries / sectors.

[0069] Application Example: Diethyl (3-pyridyl) - borane is used as a reducing agent to prepare ivabradine

[0070]

[0071] Under nitrogen protection, 100 g of compound VII was added to 1,4-dioxane (500 ml), stirred and dissolved, and then 80 g of diethyl (3-pyridyl) -borane was added. The reaction was stirred at room temperature for 5 h, and then 200 ml of water was added to quench the reaction. The mixture was concentrated under reduced pressure, extracted with ethyl acetate (500 ml × 2), dried over anhydrous sodium sulfate, the solvent was removed, and dried to obtain ivabradine.

[0072] Of course, the present invention may have many other embodiments. Without violating the spirit and essence of the present invention, those skilled in the art may make various corresponding changes and / or deformations based on the present invention. These corresponding changes and / or deformations should all fall within the scope of protection of the claims attached to the present invention.

Claims

1. A method for producing diethyl (3-pyridyl) -borane, characterized in that, The following steps are involved: With or without inert gas protection, in the presence of ethylmagnesium bromide and bromoethane, magnesium, 2-chloropropane and 3-bromopyridine are reacted in an ether solvent at 10°C to 40°C for 10 to 30 hours, and then a solution of diethylmethoxyborane or its ether solvent is added and reacted at 0°C to 10°C for 5 to 15 hours to generate diethyl(3-pyridyl)-borane; wherein the amount of magnesium, 2-chloropropane, 3-bromopyridine, diethylmethoxyborane or its ether solvent solution is greater than or equal to 1 kg; preferably, the amount of magnesium, 2-chloropropane, 3-bromopyridine, diethylmethoxyborane or its ether solvent solution is within the range of 1 kg to 500 kg.

2. The method for producing diethyl (3-pyridyl) -borane according to claim 1, characterized in that The amounts of ethylmagnesium bromide and ethyl bromide used per mole of 3-bromopyridine are 0.02 mol to 0.2 mol and 0.02 mol to 0.2 mol, respectively; preferably, the amounts of ethylmagnesium bromide and ethyl bromide used per mole of 3-bromopyridine are 0.03 mol to 0.1 mol and 0.05 mol to 0.1 mol, respectively; And / or, the amount of magnesium and 2-chloropropane used per mole of 3-bromopyridine is 1 mol to 1.5 mol, and 1 mol to 1.5 mol, respectively; preferably, the amount of magnesium and 2-chloropropane used per mole of 3-bromopyridine is 1.15 mol to 1.35 mol, and 1.05 mol to 1.25 mol, respectively; and / or, the amount of diethylmethoxyborane used per mole of 3-bromopyridine is 1 mol to 1.5 mol; preferably, the amount of diethylmethoxyborane used per mole of 3-bromopyridine is 1 mol to 1.25 mol; And / or, the amount of the ether solvent used per mole of 3-bromopyridine is 0.2 kg to 2 kg; preferably, the amount of the ether solvent used per mole of 3-bromopyridine is 0.4 kg to 1 kg.

3. The method for producing diethyl (3-pyridyl) borane according to claim 1 or 2, characterized in that The inert gas is nitrogen or argon; and / or the ether solvent is tetrahydrofuran; and / or the solution of diethylmethoxyborane in an ether solvent is a solution of diethylmethoxyborane in tetrahydrofuran.

4. The method for producing diethyl(3-pyridyl)-borane according to claim 1 or 2, wherein The reaction steps of magnesium, 2-chloropropane and 3-bromopyridine in an ether solvent are as follows: magnesium and 2-chloropropane react at 25° C. to 35° C. for 5 to 20 hours, then 3-bromopyridine is added and reacted at 20° C. to 30° C. for 5 to 10 hours; and / or, the reaction temperature of adding the solution of diethylmethoxyborane or its ether solvent is 0° C. to 5° C.; and / or, the reaction time of adding the solution of diethylmethoxyborane or its ether solvent is 7.5 hours to 15 hours.

5. The method for producing diethyl (3-pyridyl) -borane according to claim 1 or 2, characterized in that, The method further comprises the following post-processing steps: adding hydrochloric acid to quench the reaction, allowing the mixture to stand, separating the liquids, taking the organic phase, drying it without drying or adding anhydrous sodium sulfate, distilling it under reduced pressure until no fraction is obtained, adding isopropanol, stirring and maintaining the temperature at 60° C. to 70° C., then cooling the temperature to 5° C., precipitating a solid, centrifuging or filtering, and drying the solid to obtain diethyl(3-pyridyl)-borane; Preferably, the concentration of the hydrochloric acid is 12 wt% to 38 wt%.

6. A diethyl (3-pyridyl) - borane product, characterized in that, The diethyl (3-pyridyl) -borane is prepared by the production method according to any one of claims 1 to 5, and the HPLC purity of the diethyl (3-pyridyl) -borane is ≥99.0%.

7. The high performance liquid chromatography detection method of the diethyl (3-pyridyl) -borane product according to claim 6, characterized in that: The chromatographic conditions of the high performance liquid chromatography detection method include: Chromatographic column: C18 column or its equivalent; Mobile phase A: water; mobile phase B: acetonitrile; Perform gradient elution according to the following program: Alternatively, perform a gradient elution as follows: Detection wavelength: 180-280 nm; preferably, the detection wavelength is 205 nm or 268 nm.

8. The high performance liquid chromatography detection method according to claim 7, wherein The chromatographic column is a Kinetex C18 chromatographic column; and / or the specifications of the chromatographic column are: 4.6 mm×150 mm, 5 μm.

9. The high performance liquid chromatography detection method according to claim 7, wherein Column temperature: 15°C to 45°C; preferably, the column temperature is 40°C to 45°C; and / or, injection volume: 0.5 μl to 25 μl; preferably, the injection volume is 10 μl; And / or, flow rate: 0.1 ml / min to 2 ml / min; preferably, the flow rate is 1.0 ml / min to 1.5 ml / min.

10. The high performance liquid chromatography detection method according to claim 7, characterized in that: The high performance liquid chromatography detection method is a qualitative detection or a quantitative detection; preferably, the high performance liquid chromatography detection method performs quantitative detection according to the internal standard method, the external standard method or the peak area normalization method.

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