A method for synthesizing (4R)-4-(4'-nitrophenyl)-4-hydroxy-2-butanone based on molecular printing technology

Abstract

This invention discloses a method for synthesizing (4R)-4-(4'-nitrophenyl)-4-hydroxy-2-butanone based on molecular printing technology, comprising the following steps: Step 1: Mixing L-proline, acetone, and dimethyl sulfoxide uniformly to obtain solution A; mixing p-nitrobenzaldehyde and dimethyl sulfoxide uniformly to obtain solution B; Step 2: Assembling and constructing a molecular printing flow chemistry apparatus, setting parameters, starting the apparatus, and collecting the reaction solution after 2 hours of reaction; Step 3: Adding a quencher to the reaction solution obtained in Step 2 to quench the reaction, and extracting the reaction product multiple times, combining the organic phases, and purifying to obtain the (4R)-4-(4'-nitrophenyl)-4-hydroxy-2-butanone.

Description

Technical Field

[0001] This invention relates to the field of asymmetric reaction technology, specifically to a method for synthesizing (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone based on molecular printing technology. Background Technology

[0002] Aldol condensation is one of the most important methods for forming C-C bonds, and its asymmetric catalytic reaction has attracted widespread attention from organic chemists. Due to the low cost, availability, and low toxicity of small organic molecule catalysts, it has become increasingly important. Among these, the asymmetric aldol reaction catalyzed by proline can yield enantioselective products with over 96% selectivity. However, its synthesis methods remain traditional organic chemical synthesis methods. These methods suffer from low safety, wide reaction time distributions, and uneven reaction temperatures and reactants, resulting in poor heat transfer, low product yields, and cumbersome operation. Summary of the Invention

[0003] To address the aforementioned shortcomings of existing technologies, the present invention aims to provide a method for synthesizing (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone based on molecular printing technology. This method solves the problems of low safety, wide reaction time distribution, uneven heating of reactants, uneven mixing of reactants, resulting in poor heat transfer during the reaction, low product yield, and cumbersome operation in existing (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone synthesis methods.

[0004] To solve the above-mentioned technical problems, the present invention adopts the following technical solution:

[0005] A method for synthesizing (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone based on molecular printing technology includes the following steps:

[0006] Step 1: Mix L-proline, acetone, and dimethyl sulfoxide evenly to obtain solution A; mix p-nitrobenzaldehyde and dimethyl sulfoxide evenly to obtain solution B;

[0007] Step 2: Assemble and build the molecular printing flow chemistry apparatus, set the parameters, start the apparatus, and collect the reaction solution after 2 hours of reaction;

[0008] Step 3: Add a quencher to the reaction solution obtained in Step 2 to quench the reaction, and extract the reaction product multiple times. After combining the organic phases, purify the product to obtain the (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone.

[0009] Preferably, in solution A of step 1, the concentration of acetone is 4.00 mol / L to 5.00 mol / L.

[0010] Preferably, in solution B of step 1, the mass range of p-nitrobenzaldehyde is 0.20 g to 0.25 g.

[0011] Preferably, in the molecular printing flow chemistry device, the microfluidic chip temperature parameter is 30℃~40℃, the flow rate of injection pump 1 is 0.05mL / min, and the flow rate of injection pump 2 is 0.05mL / min.

[0012] Preferably, the quenching agent is a saturated aqueous solution of ammonium chloride.

[0013] Preferably, in step 3, the purification process includes the following steps:

[0014] The combined organic phases were separated by column chromatography using a stationary phase and a mobile phase; wherein the stationary phase was silica gel; and the mobile phase was a mixture of ethyl acetate and petroleum ether, and V 乙酸乙酯 V 石油醚 = 1:4.

[0015] Preferably, the molecular printing flow chemistry device is the Xinshuguang flow chemistry teaching device.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] 1. This invention uses a molecularly printed flow chemistry device to conduct the reaction, integrating and simplifying the original complex organic reaction, making the reaction operation safer. By controlling the flow rate of the fluid pump, time, temperature of the reaction tank, and other conditions such as light, microwave, and ultrasound, the reactant solution is made to pass through the reaction tank at a constant flow rate at a set temperature, achieving continuous reaction. Furthermore, the method described in this invention improves the utilization rate of raw material atoms, produces fewer by-products, and the product has not only high yield but also high purity.

[0018] 2. Existing technologies often use the Aldol condensation reaction of p-nitrobenzaldehyde and acetone as an undergraduate teaching and research training experiment to help students understand the application of simple organic molecules as catalysts in asymmetric organic synthesis. However, existing technologies generally employ traditional organic chemical synthesis methods, which are less safe, more cumbersome, and do not provide students with a direct understanding of the reaction process. This invention utilizes a molecularly printed flow chemistry device to conduct the reaction, cleverly trading time for spatial visualization. This not only simplifies the experimental operation and improves product yield and purity, allowing students to gain positive feedback from the experiment, but also enables them to intuitively understand the reaction process. This allows students to more accurately grasp the reaction principle and has excellent application prospects. Attached Figure Description

[0019] Figure 1The chiral product (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone synthesized in Example 1 via an asymmetric aldol reaction using molecular printing technology (flow chemistry teaching device) was developed in solvent (V). 乙酸乙酯 V 石油醚 =1:4), determination by TLC thin-layer chromatography under ultraviolet light (254nm) conditions.

[0020] Figure 2 The image shows the hydrogen NMR spectrum of the product from Example 2.

[0021] Figure 3 The image shows the infrared spectrum of the product in Example 3.

[0022] Figure 4 The values ​​represent the optical rotation and specific rotation of the product in Example 4.

[0023] Figure 5 A diagram illustrating the asymmetric aldol reaction phenomenon for molecularly printed flow chemistry equipment. Detailed Implementation

[0024] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0025] I. A method for synthesizing (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone based on molecular printing technology, comprising the following steps:

[0026] Step 1: Mix L-proline, acetone, and dimethyl sulfoxide evenly to obtain solution A; mix p-nitrobenzaldehyde and dimethyl sulfoxide evenly to obtain solution B;

[0027] Step 2: Assemble and build the molecular printing flow chemistry apparatus, set the parameters, start the apparatus, and collect the reaction solution after 2 hours of reaction;

[0028] Step 3: Add a quencher to the reaction solution obtained in Step 2 to quench the reaction, and extract the reaction product multiple times. After combining the organic phases, purify the product to obtain the (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone.

[0029] Preferably, in solution A of step 1, the concentration of acetone is 4.00 mol / L to 5.00 mol / L.

[0030] Preferably, in solution B of step 1, the mass range of p-nitrobenzaldehyde is 0.20 g to 0.25 g.

[0031] Preferably, in the molecular printing flow chemistry device, the microfluidic chip temperature parameter is 30℃~40℃, the flow rate of injection pump 1 is 0.05mL / min, and the flow rate of injection pump 2 is 0.05mL / min.

[0032] Preferably, the quenching agent is a saturated aqueous solution of ammonium chloride.

[0033] Preferably, in step 3, the purification process includes the following steps:

[0034] The combined organic phases were separated by column chromatography using a stationary phase and a mobile phase; wherein the stationary phase was silica gel; and the mobile phase was a mixture of ethyl acetate and petroleum ether, and V 乙酸乙酯 V 石油醚 = 1:4.

[0035] Preferably, the molecular printing flow chemistry device is the Xinshuguang flow chemistry teaching device.

[0036] II. Examples and Comparative Examples

[0037] Example 1

[0038] A) Weigh 0.0519 g of L-proline, measure 1.2 mL of acetone and 2.4 mL of dimethyl sulfoxide, and mix them evenly in an Erlenmeyer flask to prepare solution A. Weigh 0.2268 g of p-nitrobenzaldehyde and measure 2.4 mL of dimethyl sulfoxide, and mix them evenly in an Erlenmeyer flask to prepare solution B. Assemble the flow chemistry teaching apparatus, plug in the power supply, clean the microfluidic chip with distilled water, and pre-set the microfluidic chip temperature to 30℃ and the flow rate parameters of syringe pump 1 and syringe pump 2 to 0.05 mL / min and 0.05 mL / min, respectively. Connect the inlet tube of syringe pump 1 to the Erlenmeyer flask containing solution A, and connect the inlet tube of syringe pump 2 to the Erlenmeyer flask containing solution B. Start the apparatus according to the pre-set parameters. After reacting for 2 hours, collect the reaction solution.

[0039] B) Take a chromatography plate and draw a horizontal line from left to right 1 cm from the bottom with a pencil (draw the line lightly, do not tear the chromatography plate). Mark three points at equal intervals along the line. Using different capillaries, spot the prepared p-nitrobenzaldehyde, racemic reaction solution, and reaction solution onto the three marked points respectively. After spotting, use tweezers to place the chromatography plate in the developing jar, immersing the side with the drawn line in the developing solvent (developing solvent V). 石油 :V 乙酸乙酯 =4:1). Observe the chromatography plate. When the liquid level on the plate reaches 1 cm from the top, use tweezers to remove the plate. Observe the sample: Use tweezers to place the developed chromatography plate under a UV lamp (254 nm) and observe the number and position of the fluorescent spots on the plate.

[0040] Example 2

[0041] A) Weigh 0.0519 g of L-proline, measure 1.2 mL of acetone and 2.4 mL of dimethyl sulfoxide, and mix them evenly in an Erlenmeyer flask to prepare solution A. Weigh 0.2268 g of p-nitrobenzaldehyde and measure 2.4 mL of dimethyl sulfoxide, and mix them evenly in an Erlenmeyer flask to prepare solution B. Assemble the flow chemistry teaching apparatus, plug in the power supply, clean the microfluidic chip with distilled water, and pre-set the microfluidic chip temperature to 30℃ and the flow rate parameters of syringe pump 1 and syringe pump 2 to 0.05 mL / min and 0.05 mL / min, respectively. Connect the inlet tube of syringe pump 1 to the Erlenmeyer flask containing solution A, and connect the inlet tube of syringe pump 2 to the Erlenmeyer flask containing solution B. Start the apparatus according to the pre-set parameters. After reacting for 2 hours, collect the reaction solution. Add 10 mL of saturated ammonium chloride aqueous solution to the reaction solution to quench the reaction, and add 10 mL of water and ethyl acetate (20 mL × 3) for extraction in three portions. Combine the organic phases. Excess anhydrous sodium sulfate was added to the organic phase, dried, filtered, and rotary evaporated to obtain the reaction residue. The reaction residue was then separated by column chromatography (stationary phase: silica gel, mobile phase: V). 乙酸乙酯 V 石油醚 =1:4), the eluent is rotary evaporated until a viscous liquid is obtained, and the product is obtained.

[0042] B) Take a small amount of the product and completely dissolve it in CDCl3 (containing 0.03% v / v TMS) for nuclear magnetic resonance spectroscopy characterization.

[0043] Example 3

[0044] A) Weigh 0.0519 g of L-proline, measure 1.2 mL of acetone and 2.4 mL of dimethyl sulfoxide, and mix them evenly in an Erlenmeyer flask to prepare solution A. Weigh 0.2268 g of p-nitrobenzaldehyde and measure 2.4 mL of dimethyl sulfoxide, and mix them evenly in an Erlenmeyer flask to prepare solution B. Assemble the flow chemistry teaching apparatus, plug in the power supply, clean the microfluidic chip with distilled water, and pre-set the microfluidic chip temperature to 30℃ and the flow rate parameters of syringe pump 1 and syringe pump 2 to 0.05 mL / min and 0.05 mL / min, respectively. Connect the injection tube of syringe pump 1 to the Erlenmeyer flask containing solution A, and connect the injection tube of syringe pump 2 to the Erlenmeyer flask containing solution B. Start the apparatus according to the pre-set parameters. After reacting for 2 hours, collect the reaction solution. Add 10 mL of saturated ammonium chloride aqueous solution to the reaction solution to quench the reaction, and add 10 mL of water and ethyl acetate (20 mL × 3) for extraction in three portions. Combine the organic phases. Excess anhydrous sodium sulfate was added to the organic phase, dried, filtered, and rotary evaporated to obtain the reaction residue. The reaction residue was then separated by column chromatography (stationary phase: silica gel, mobile phase: V). 乙酸乙酯 V 石油醚 =1:4), the resulting eluent is rotary evaporated until it becomes a viscous liquid, and the product is obtained.

[0045] B) Take a small amount of the product for infrared spectroscopy characterization.

[0046] Example 4

[0047] A) Weigh 0.0519 g of L-proline, measure 1.2 mL of acetone and 2.4 mL of dimethyl sulfoxide, and mix them evenly in an Erlenmeyer flask to prepare solution A. Weigh 0.2268 g of p-nitrobenzaldehyde and measure 2.4 mL of dimethyl sulfoxide, and mix them evenly in an Erlenmeyer flask to prepare solution B. Assemble the flow chemistry teaching apparatus, plug in the power supply, clean the microfluidic chip with distilled water, and pre-set the microfluidic chip temperature to 30℃ and the flow rate parameters of syringe pump 1 and syringe pump 2 to 0.05 mL / min and 0.05 mL / min, respectively. Connect the injection tube of syringe pump 1 to the Erlenmeyer flask containing solution A, and connect the injection tube of syringe pump 2 to the Erlenmeyer flask containing solution B. Start the apparatus according to the pre-set parameters. After reacting for 2 hours, collect the reaction solution. Add 10 mL of saturated ammonium chloride aqueous solution to the reaction solution to quench the reaction, and add 10 mL of water and ethyl acetate (20 mL × 3) for extraction in three portions. Combine the organic phases. Excess anhydrous sodium sulfate was added to the organic phase, dried, filtered, and rotary evaporated to obtain the reaction residue. The reaction residue was then separated by column chromatography (stationary phase was silica gel, mobile phase was V ethyl acetate: V petroleum ether = 1:4). The resulting eluent was rotary evaporated to a viscous liquid to obtain the product.

[0048] B) Weigh 65.7 mg of the product, dissolve it in dichloromethane and make up to 100.00 mL in a volumetric flask. Then use a polarimeter to detect the optical rotation α and calculate its specific rotation [α].

[0049] Table 1

[0050]

[0051] Examples 5-10 and Comparative Examples 1-4 were prepared using the method described in Example 1, and the yields of the products were calculated and obtained. The starting material ratios for Comparative Example 5 in Table 1 were used, but (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone was prepared using conventional chemical synthesis steps. The specific preparation steps are as follows:

[0052] A) Prepare a clean, dry 50mL round-bottom flask, add a magnetic stir bar beforehand, weigh out 0.0519g of L-proline, 4.8mL of dimethyl sulfoxide, and 1.2mL of acetone, and add them sequentially to the round-bottom flask. Fix the flask above the magnetic stirrer with an iron stand and start stirring. After stirring for 15 minutes, add 0.2268g of p-nitrobenzaldehyde. After reacting for 2 hours, collect the reaction solution. Add 10mL of saturated ammonium chloride aqueous solution to the reaction solution to quench the reaction, and add 10mL of water and ethyl acetate (20mL × 3) for extraction in three portions, combining the organic phases. Add excess anhydrous sodium sulfate to the organic phase, dry, filter, and rotary evaporate to obtain the reaction residue. Then, perform column chromatography on the reaction residue (stationary phase: silica gel, mobile phase: V ethyl acetate: V petroleum ether = 1:4). Rotary evaporate the resulting eluent to a viscous liquid to obtain the product.

[0053] B) 0.1736 g of product was weighed, and the yield was calculated to be 55.30%.

[0054] Comparative Example 2

[0055] 0.2268 g of p-nitrobenzaldehyde was added to a 25 mL round-bottom flask. A magnetic stir bar was added, and while stirring, 1.2 mL of acetone, 4 mL of dimethyl sulfoxide, and 0.0519 g of L-proline were added sequentially. The mixture was stirred at room temperature for 2 h. 10 mL of saturated ammonium chloride aqueous solution was added to the reaction solution to quench the reaction, and water (10 mL) and ethyl acetate (20 mL) were added in three portions for extraction. The organic phases were combined. Excess anhydrous sodium sulfate was added to the organic phase for drying, followed by filtration and rotary evaporation to obtain the reaction residue. The reaction residue was then separated by column chromatography (stationary phase: silica gel, mobile phase: V ethyl acetate: V petroleum ether = 1:4). The eluent was rotary evaporated to a viscous liquid to obtain the product, with a yield of approximately 60%.

[0056] In the process of preparing products using conventional chemical synthesis methods, students cannot simultaneously observe the color changes of the reaction solution at different reaction times because the reaction process is often fleeting, the contrast between the phenomena before and after the experiment is not obvious, and it is difficult to fully present the results. Furthermore, the experimental conditions are not easily controlled. The method provided by this invention allows students to simultaneously observe experimental phenomena at different reaction stages in the reaction vessel. Simultaneously, the Xinshuguang flow chemistry teaching device can precisely control experimental conditions such as temperature, which is beneficial to the reaction. In addition, the yield of the product prepared by the method provided by this invention is higher than that prepared using conventional chemical synthesis methods.

[0057] III. Results Analysis

[0058] Figure 1The chiral product (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone synthesized in Example 1 via an asymmetric aldol reaction using molecular printing technology (flow chemistry teaching device) is in the developing solvent (V 乙酸乙酯 V 石油醚 =1:4), determination by TLC thin-layer chromatography under UV lamp (254nm). Point ① is the starting material p-nitrobenzaldehyde, R f The value is 0.8; point ② is the reaction solution of p-nitrobenzaldehyde and acetone catalyzed by pyrrolidine, which has 3 points after development, R f =0.8 indicates it is p-nitrobenzaldehyde, R f The point at which R = 0.5 represents a by-reaction product. f Point 0.2 represents (4S)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone; point ③ represents the reaction solution of L-proline-catalyzed p-nitrobenzaldehyde and acetone using a flow chemistry apparatus. After development, two points are observed, indicating the reaction is complete and a new, highly polar substance (R) is present. f =0.2) was generated, and it was initially identified as the target product (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone. Using existing conventional organic synthesis methods, students cannot observe the start time of the reaction or the detailed process of the reaction as in a flow chemistry apparatus.

[0059] Figure 2 This is the determination of the 400MHz NMR spectrometry characterization image of the chiral product (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone synthesized via an asymmetric aldol reaction using a molecular printing flow chemistry apparatus in Example 2. The obtained (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone was analyzed using CDCl3 (containing 0.03% v / v TMS) as solvent and calibrated to 0 by the chemical shift of hydrogen on the TMS. 11H NMR characterization. The 1H NMR spectrum shows: the first peak at 8.20 (d, J = 8.7 Hz, 2H), a doublet, corresponds to the hydrogen at the f-position of the benzene ring and its symmetrical position in the (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone structure, a total of 2 hydrogens; the second peak at 7.54 (d, J = 8.7 Hz, 2H), a doublet, corresponds to the hydrogen at the e-position of the benzene ring and its symmetrical position in the (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone structure, a total of 2 hydrogens; the third peak at 5.27 (d, J = 8.7 Hz, 1H), a triplet, corresponds to the (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone structure. The fourth peak at 4.73 (s, 1H) corresponds to the hydrogen at the c-position of the hydroxyl group in the (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone structure, with one hydrogen in total. The fifth peak at 2.85 (m, 2H) corresponds to the hydrogen at the b-position of the (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone structure, with two hydrogens in total. The sixth peak at 2.22 (s, 3H) corresponds to the hydrogen at the a-position of the (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone structure, with three hydrogens in total. The obtained spectrum matches the structure of the target product, indicating that the reaction can be achieved using this flow chemistry apparatus, and the corresponding target product can be successfully synthesized.

[0060] Figure 3 This is the infrared spectroscopic characterization image of (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone, the chiral product synthesized via an asymmetric aldol reaction using a molecularly printed flow chemistry apparatus in Example 3. The wavenumber in the image is 3394.93 cm⁻¹. -1 The characteristic peak for hydroxyl groups is 1715.21 cm⁻¹. -1 The characteristic peak for carbonyl groups is 1610.25 cm⁻¹. -1 This is the characteristic peak of the stretching vibration of the carbon-carbon double bond in the benzene ring, with a wavenumber of 1530.76 cm⁻¹. -1 The peaks are characteristic of the antisymmetric stretching vibration of nitro groups. The infrared spectrum obtained can be used to identify the characteristic functional groups contained in the synthesized product, and the results show that the obtained product is consistent with the target product.

[0061] Figure 4This section describes the determination of the optical rotation and specific rotation of (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone, the chiral product synthesized via an asymmetric aldol reaction using molecular printing technology (flow chemistry teaching device) in Example 4. 65.7 mg of (4R)-4-(4′-nitrophenyl)-4-hydroxy-2-butanone was weighed, dissolved in dichloromethane, and diluted to 100.00 mL in a volumetric flask. The process was repeated to prepare a control solution of the racemic (4′-nitrophenyl)-4-hydroxy-2-butanone. The optical rotation was measured using a 10 cm test tube. The measured optical rotation α1 of the racemic (4′-nitrophenyl)-4-hydroxy-2-butanone was 0. The optical rotation α2 of (4'-nitrophenyl)-4-hydroxy-2-butanone is 0.0245. Based on [α] = α / (l×c), the specific optical rotation [α1] of (4'-nitrophenyl)-4-hydroxy-2-butanone is calculated to be 0 (c = 0.0657, CH2Cl2). Therefore, the specific optical rotation [α2] of (4R)-4-(4'-nitrophenyl)-4-hydroxy-2-butanone is +37.29 (c = 0.0657, CH2Cl2). Refer to the reference value [α2]. 20 D = +41.1 (c = 0.68, CH2Cl2), indicating that the target product can be obtained by promoting the reaction through a flow chemistry apparatus, which is chiral.

[0062] Figure 5 This experiment uses molecular printing technology (a flow chemistry teaching device) to demonstrate the changes in the asymmetric aldol reaction over time. When solutions A and B are first mixed, they are colorless, indicating that the reaction will not occur immediately. After a period of time, they gradually turn light orange, indicating the start of the reaction and its gradual progress. As time continues, the color of the reaction solution slowly deepens to orange-red, showing the entire reaction process. This allows students to directly observe the extent of the organic reaction, effectively stimulating their enthusiasm for learning and enhancing their interest and motivation in organic chemistry experiments.

[0063] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit the technical solutions. Those skilled in the art should understand that any modifications or equivalent substitutions to the technical solutions of the present invention without departing from the spirit and scope of the present invention should be covered within the scope of the claims of the present invention.

Claims

1. A method for synthesizing (4R)-4-(4'-nitrophenyl)-4-hydroxy-2-butanone based on molecular printing technology, characterized in that, Includes the following steps: Step 1: Mix L-proline, acetone and dimethyl sulfoxide evenly to obtain solution A, wherein the concentration of acetone is 4.00 mol / L~5.00 mol / L; mix p-nitrobenzaldehyde and dimethyl sulfoxide evenly to obtain solution B, wherein the mass range of p-nitrobenzaldehyde is 0.2000 g~0.2500 g; Step 2: Assemble and build the molecular printing flow chemistry device. The molecular printing flow chemistry device is the Xinshuguang flow chemistry teaching device. Set the microfluidic chip temperature parameter to 30℃, the flow rate of the syringe pump 1 used to deliver solution A to 0.05mL / min, the flow rate of the syringe pump 2 used to deliver solution B to 0.05mL / min, start the device, and collect the reaction solution after 2 hours of reaction. Step 3: Add saturated ammonium chloride aqueous solution to the reaction solution obtained in Step 2 to quench the reaction, extract the reaction product multiple times, combine the organic phases, and use silica gel as the stationary phase and ethyl acetate-petroleum ether mixture with a volume ratio of 1:4 as the mobile phase for column chromatography separation and purification to obtain the (4R)-4-(4'-nitrophenyl)-4-hydroxy-2-butanone.

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