阅读说明：本技术 一种5-氯-2,2-二甲基戊酸异丁酯的制备方法 (Preparation method of isobutyl 5-chloro-2, 2-dimethylpentanoate ) 是由 沈浩 吴珊 沈新良 袁鸿威 张宝华 刘莹 于 2020-12-28 设计创作，主要内容包括：本发明涉及一种5-氯-2,2-二甲基戊酸异丁酯的制备方法,该制备方法包括A相与B相换热处理与反应,相继加入异丁酸异丁酯C相、1,3-溴氯丙烷D相、稀盐酸E相进行反应,在淬灭模块中淬灭,后处理得到5-氯-2,2-二甲基戊酸异丁酯。本发明用正丁基锂代替金属锂,降低了反应过程中的安全风险；采用连续流微通道反应器,显著缩短反应时间,极大地提升了反应效率；产物纯度达到97％以上,收率高达91％以上。(The invention relates to a preparation method of 5-chloro-2, 2-dimethyl isobutyl valerate, which comprises the steps of carrying out heat exchange treatment and reaction on a phase A and a phase B, sequentially adding an isobutyl isobutyrate phase C, a 1, 3-bromochloropropane phase D and a dilute hydrochloric acid phase E for reaction, quenching in a quenching module, and carrying out aftertreatment to obtain the 5-chloro-2, 2-dimethyl isobutyl valerate. According to the invention, metal lithium is replaced by n-butyl lithium, so that the safety risk in the reaction process is reduced; by adopting the continuous flow microchannel reactor, the reaction time is obviously shortened, and the reaction efficiency is greatly improved; the purity of the product reaches more than 97 percent, and the yield reaches more than 91 percent.)

1. A preparation method of isobutyl 5-chloro-2, 2-dimethylpentanoate is characterized by comprising the following preparation steps:

I. dissolving diisopropylamine in an organic solvent to obtain a diisopropylamine organic solution phase A with the concentration of 10-50% by weight;

dissolving n-butyllithium in n-hexane to obtain a diisopropylamine n-hexane solution B phase with the concentration of 15-25% by weight;

pumping the phase A and the phase B into a heat exchange module of the microchannel reactor by a metering pump, and carrying out heat exchange treatment at the temperature of-10 ℃ to-30 ℃;

II. Respectively feeding the phase A obtained in the step I and the phase B into a first reaction module of a microchannel reactor at the flow rates of 50.0-200.0 g/min and 40.0-80.0 g/min by a metering pump, reacting for 6-30 s at the temperature of-30 to +15 ℃, and discharging the reaction liquid into a second reaction module;

feeding isobutyl isobutyrate C phase into a second reaction module by a metering pump at a flow rate of 20.0-30.0 g/min, reacting the isobutyl isobutyrate C phase with a reaction liquid discharged from a first reaction module at a temperature of + 8-18 ℃ for 8-30 s, and then discharging the reaction liquid into a third reaction module;

sending the 1, 3-bromochloropropane D phase to a third reaction module by a metering pump at the flow rate of 30.0-40.0 g/min, reacting the 1, 3-bromochloropropane D phase with reaction liquid discharged from the second reaction module at the temperature of + 7-18 ℃ for 6-25 s, and then discharging the reaction liquid to a quenching module;

III, feeding the dilute hydrochloric acid E phase into a quenching module by a metering pump at the flow rate of 35.0-50.0 g/min, reacting the dilute hydrochloric acid E phase with a reaction liquid discharged from a third reaction module at the temperature of + 5-10 ℃ for 6-7 s, and carrying out post-treatment to obtain the 5-chloro-2, 2-dimethyl isobutyl valerate.

2. The method according to claim 1, wherein the organic solvent is one or more organic solvents selected from the group consisting of tetrahydrofuran, 2-methyltetrahydrofuran, n-hexane, cyclohexane, heptane and petroleum ether.

3. The method according to claim 1, wherein the molar ratio of the reactants of the phase A, the phase B, the phase C, the phase D and the phase E is 1.0-5.0: 1.0-3.0: 1.0: 1.0-3.0: 1.0 to 5.0.

4. The method according to claim 1, wherein the E phase concentration of the dilute hydrochloric acid is 0.1 to 2.0N.

5. The preparation method according to claim 1, wherein the heat exchange treatment time of the phase A and the phase B in the heat exchange module is 3-10 seconds.

6. The process of claim 1 wherein the module structure in the microchannel reactor is a t-shaped structure, a spherical structure, an umbrella-shaped structure or a heart-shaped structure.

7. The method of claim 1, wherein the metering pump is a Waukesha waukkas rotor pump, a precision miniature internal gear metering pump, a multi-plunger hydraulic diaphragm metering pump, or a high-flow high-pressure multi-plunger diaphragm pump.

8. The method according to claim 1, wherein the post-treatment is a conventional treatment of water washing, distillation and rectification.

[ technical field ] A method for producing a semiconductor device

The invention belongs to the technical field of compound synthesis. More particularly, the invention relates to a preparation method of isobutyl 5-chloro-2, 2-dimethylpentanoate.

[ background of the invention ]

Metconazole, also called as triflumizole, is a novel, broad-spectrum systemic fungicide. The bactericidal composition has excellent protection and treatment effects, low toxicity to non-target organisms, low dosage, high bactericidal activity, and excellent application prospect by combining the requirements of green prevention and control. The metconazole field application has excellent effect on the planting diseases of the grain crops such as septoria, neurospora and puccinia. The mechanism of action is C-14 demethylase inhibitor in ergosterol biosynthesis. Although the action mechanism is the same as that of other triazole bactericides, the difference of the activity spectrum is large. Compared with the traditional bactericide, the bactericide has extremely low dosage and wide range of preventing and treating cereal plant diseases.

Isobutyl 5-chloro-2, 2-dimethylpentanoate is a key intermediate for the synthesis of gemfibrozil and is also a key intermediate for the synthesis of metconazole. CN 201610308539 reports a synthesis method of 5, 5-dimethyl-2-cyanocyclopentanone, an intermediate for preparing metconazole, using isobutyl 5-chloro-2, 2-dimethylpentanoate as a starting material. The synthesis process cost, safety and operability are the keys for preparing the metconazole technical product.

US4665226a discloses a synthesis of isobutyl 5-chloro-2, 2-dimethylpentanoate prepared by a pot reaction using lithium metal, diisopropylamine, isobutyl isobutyrate and bromochloropropane, of the formula:

because lithium is flammable and explosive when meeting air, the storage and feeding are very critical, certain potential safety hazard exists in the using process, the reaction operation process is complex, the mass transfer and heat transfer efficiency of kettle type equipment is low, a plurality of reaction byproducts are produced, and the product yield is low.

Therefore, the present inventors have completed the present invention by a large number of experimental studies and analytical summaries based on the summary of the prior art.

[ summary of the invention ]

[ problem to be solved ]

The invention aims to provide a preparation method of isobutyl 5-chloro-2, 2-dimethylpentanoate.

[ solution ]

The invention is realized by the following technical scheme.

The invention relates to a preparation method of isobutyl 5-chloro-2, 2-dimethylpentanoate. The specific process flow of the preparation method is shown in figure 1.

The preparation method comprises the following preparation steps:

I. dissolving diisopropylamine in an organic solvent to obtain a diisopropylamine organic solution phase A with the concentration of 10-50% by weight;

dissolving n-butyllithium in n-hexane to obtain a diisopropylamine n-hexane solution B phase with the concentration of 15-25% by weight;

pumping the phase A and the phase B into a heat exchange module of the microchannel reactor by a metering pump, and carrying out heat exchange treatment at the temperature of-10 ℃ to-30 ℃;

II. Respectively feeding the phase A obtained in the step I and the phase B into a first reaction module of a microchannel reactor at the flow rates of 50.0-200.0 g/min and 40.0-80.0 g/min by a metering pump, reacting for 6-30 s at the temperature of-30 to +15 ℃, and discharging the reaction liquid into a second reaction module;

feeding isobutyl isobutyrate C phase into a second reaction module by a metering pump at a flow rate of 20.0-30.0 g/min, reacting the isobutyl isobutyrate C phase with a reaction liquid discharged from a first reaction module at a temperature of + 8-18 ℃ for 8-30 s, and then discharging the reaction liquid into a third reaction module;

sending the 1, 3-bromochloropropane D phase to a third reaction module by a metering pump at the flow rate of 30.0-40.0 g/min, reacting the 1, 3-bromochloropropane D phase with reaction liquid discharged from the second reaction module at the temperature of + 7-18 ℃ for 6-25 s, and then discharging the reaction liquid to a quenching module;

III, feeding the dilute hydrochloric acid E phase into a quenching module by a metering pump at the flow rate of 35.0-50.0 g/min, reacting the dilute hydrochloric acid E phase with a reaction liquid discharged from a third reaction module at the temperature of + 5-10 ℃ for 6-7 s, and carrying out post-treatment to obtain the 5-chloro-2, 2-dimethyl isobutyl valerate.

According to another preferred embodiment of the present invention, the organic solvent is one or more organic solvents selected from tetrahydrofuran, 2-methyltetrahydrofuran, n-hexane, cyclohexane, heptane or petroleum ether.

According to another preferred embodiment of the present invention, the molar ratio of the reactants of the phase A, the phase B, the phase C, the phase D and the phase E is 1.0 to 5.0: 1.0-3.0: 1.0: 1.0-3.0: 1.0 to 5.0.

According to another preferred embodiment of the present invention, the concentration of the dilute hydrochloric acid E phase is 0.1 to 2.0N.

According to another preferred embodiment of the invention, the heat exchange treatment time of the phase A and the phase B in the heat exchange module is 3-10 seconds.

According to another preferred embodiment of the present invention, the module structure in the microchannel reactor is a t-shaped structure, a spherical structure, an umbrella-shaped structure or a heart-shaped structure.

According to another preferred embodiment of the invention, the metering pump is a Waukesha rotor pump, a precision miniature internal gear metering pump, a multi-plunger hydraulic diaphragm metering pump or a high-flow high-pressure multi-plunger diaphragm pump.

According to another preferred embodiment of the present invention, the post-treatment is a conventional treatment of water washing, distillation and rectification.

The present invention will be described in more detail below.

The invention relates to a preparation method of isobutyl 5-chloro-2, 2-dimethylpentanoate.

The reaction for the preparation of isobutyl 5-chloro-2, 2-dimethylpentanoate is as follows:

in the present invention, this reaction is carried out in a microchannel reactor.

The micro-channel reactor has a large specific surface area due to the internal microstructure thereof, which can reach hundreds of times or even thousands of times of the specific surface area of the stirred tank. The microchannel reactor has heat and mass transfer capabilities to achieve instantaneous uniform mixing and heat transfer of materials, so that many reactions that cannot be achieved in conventional reactors can be achieved in the microchannel reactor.

The module structure of the microchannel reactor used in the present invention is a t-shaped structure, a spherical structure, an umbrella-shaped structure or a heart-shaped structure, which are all products currently sold in the market, such as the MRSF20 type microchannel reactor sold by Shandong Haimai chemical engineering Co., Ltd.

The preparation method comprises the following preparation steps:

I. dissolving diisopropylamine in an organic solvent to obtain a diisopropylamine organic solution phase A with the concentration of 10-50% by weight;

in the step, diisopropylamine is dissolved in an organic solvent to obtain a diisopropylamine organic solution A phase with the concentration of 10-50% by weight;

if the concentration of the diisopropylamine organic solution phase A is lower than 10% by weight, the organic solvent is used too much, the recovery cost is increased, and unnecessary waste is caused; if the concentration of the phase A of the diisopropylamine organic solution is higher than 50 percent by weight, the concentration of the diisopropylamine is too high, a material transfer pump with matched flow rate is required to be selected during feeding, or the concentration of the diisopropylamine organic solution can be higher than 50 percent, but a normal hexane solution of n-butyllithium with lower concentration is selected; therefore, it is reasonable that the concentration of the phase A of the diisopropylamine organic solution is 10 to 50% by weight, preferably 16 to 44%, more preferably 20 to 38%.

The diisopropylamine used in the present invention is a product currently marketed, for example, by the company Jinan Shuangying chemical Co., Ltd under the trade name diisopropylamine.

The organic solvent used in the present invention is one or more organic solvents selected from the group consisting of tetrahydrofuran, 2-methyltetrahydrofuran, n-hexane, cyclohexane, heptane and petroleum ether, which are currently commercially available products, such as tetrahydrofuran sold under the trade name tetrahydrofuran by Shandong Xinbaihe chemical technology Co., Ltd, 2-methyltetrahydrofuran sold under the trade name 2-methyltetrahydrofuran by Jinan Mingyu chemical Co., Ltd, and the like.

Dissolving n-butyllithium in n-hexane to obtain a diisopropylamine n-hexane solution B phase with the concentration of 15-25% by weight; or using n-butyl lithium n-hexane solution with the concentration of 15-25% by weight sold in the market at present.

The concentration of the B phase of the diisopropylamine n-hexane solution is suitably 15 to 25% by weight, preferably 17 to 23%, more preferably 19 to 21%.

Pumping the phase A and the phase B into a heat exchange module of the microchannel reactor by a metering pump, and carrying out heat exchange treatment at the temperature of-10 ℃ to-30 ℃;

in the present invention, the main effect of this heat exchange treatment is to lower the temperature to be the same as or close to the reaction temperature in the next step, so that the reaction is more stable.

If the temperature of the heat exchange treatment is higher than-10 ℃, the mixed solution of the phase A and the phase B needs to enter slowly on the premise of ensuring the temperature of the next step, otherwise, the temperature is over-high, and impurities are generated; if the temperature of the heat exchange treatment is lower than-30 ℃, the temperature drop is too low, and the reaction time of the next step is prolonged; therefore, the temperature of this heat exchange treatment is suitably from-10 ℃ to-30 ℃, preferably from-15 ℃ to-24 ℃, more preferably from-18 ℃ to-21 ℃.

The heat exchange processing time of the phase A and the phase B in the heat exchange module is 3-10 seconds, and if the heat exchange processing time exceeds the range, the heat exchange processing time is not preferable, because the time is less than 3 seconds, the heat exchange is possibly insufficient, and the time is wasted more than 10 seconds.

The metering pump used in the present invention is a Waukesha waukkasa rotor pump, a precision miniature internal gear metering pump, a multi-plunger hydraulic diaphragm metering pump, or a high-flow high-pressure multi-plunger diaphragm pump, all of which are currently marketed products, such as the Waukesha waukkasa rotor pump sold by nerett fluid equipment ltd.

The metering pump used in this step is the same as the metering pump to be referred to below, and therefore, the description thereof is omitted.

II. Respectively feeding the phase A obtained in the step I and the phase B into a first reaction module of a microchannel reactor at the flow rates of 50.0-200.0 g/min and 40.0-80.0 g/min by a metering pump, reacting for 6-30 s at the temperature of-30 to +15 ℃, and discharging the reaction liquid into a second reaction module;

in the present invention, the following reaction is carried out in the first reaction module:

in the step, when the flow rate of the phase B is 40.0-80.0 g/min, if the flow rate of the phase A is lower than 50.0g/min, the amount of diisopropylamine is too small, butyl lithium is not completely reacted, and butyl lithium waste is caused; if the flow rate of the phase A is higher than 200.0g/min, the diisopropylamine is excessive, and the diisopropylamine is wasted; accordingly, it is appropriate that the flow rate of phase A is 50.0 to 200.0g/min, preferably 80.0 to 170.0g/min, more preferably 100.0 to 150.0 g/min;

similarly, when the flow rate of the phase A is 50.0-200.0 g/min, if the flow rate of the phase B is lower than 40.0g/min, the butyl lithium is insufficient, and the diisopropylamine is wasted; if the flow rate of the phase B is higher than 80.0g/min, the amount of diisopropylamine is too small, butyl lithium is not completely reacted, and butyl lithium waste is caused; accordingly, it is appropriate that the flow rate of the B phase is 40.0 to 80.0g/min, preferably 46.0 to 70.0g/min, more preferably 50.0 to 62.0 g/min;

it is not preferable to carry out the reaction in the first reaction module at a temperature exceeding the range because the temperature is lower than 25 c, and energy is wasted although the reaction is also possible. The temperature difference between the reaction temperature and the next reaction is too large when the temperature is higher than 10 ℃, and the reaction is not stable; preferably, the reaction temperature of this reaction is-25 to +10 deg.C, more preferably, the reaction temperature of this reaction is-20 to +5 deg.C.

Likewise, it is unacceptable to conduct the reaction in the first reaction module for a time period exceeding the range because the time period below 10 seconds is too short to complete the reaction. Above 26s, the time is too long, not necessary; preferably, the reaction time of the reaction is 10-26 s, and more preferably, the reaction time of the reaction is 14-20 s.

Preferably, the phase A reacts for 10-26 s at a reaction temperature of-25 to +10 ℃ in the first reaction module at a flow rate of 80.0-170.0 g/min and the phase B at a flow rate of 46.0-70.0 g/min.

More preferably, the phase A reacts for 14-20 s at a reaction temperature of-20 to +5 ℃ in the first reaction module at a flow rate of 100.0 to 150.0g/min and the phase B at a flow rate of 50.0 to 62.0 g/min.

Feeding isobutyl isobutyrate C phase into a second reaction module by a metering pump at a flow rate of 20.0-30.0 g/min, reacting the isobutyl isobutyrate C phase with a reaction liquid discharged from a first reaction module at a temperature of + 8-18 ℃ for 8-30 s, and then discharging the reaction liquid into a third reaction module;

in the present invention, the following reaction is carried out in the second reaction module:

in this step, if the flow rate of the isobutyl isobutyrate C phase is lower than 20.0g/min, the intermediate lithium diisopropylamide is in excess, resulting in waste; if the flow rate of the isobutyl isobutyrate C phase is higher than 30.0g/min, isobutyl isobutyrate is wasted; therefore, the flow rate of the isobutyl isobutyrate C phase is suitably from 20.0 to 30.0g/min, preferably from 22.0 to 28.0g/min, more preferably from 24.0 to 26.0 g/min;

it is not preferable that the temperature of the reaction carried out in the second reaction module exceeds the range because energy is wasted below 15 ℃. Above 5 ℃, the temperature difference is too large, and the reaction is not stable; preferably, the temperature of the reaction is between +5 and-15 deg.C, more preferably, the temperature of the reaction is between +2 and-12 deg.C.

Likewise, it is not preferable to conduct the reaction in the second reaction module for a time exceeding the range because the time below 10s is too short to complete the reaction. Above 26s, the time is too long, not necessary; preferably, the reaction time is 10-26 s, and more preferably, the reaction time is 13-22 s.

Preferably, the isobutyl isobutyrate C phase is fed into the second reaction module at a flow rate of 22.0-28.0 g/min and reacts at a temperature of + 5-15 ℃ for 10-26 s.

More preferably, the isobutyl isobutyrate C phase is fed to the second reaction module at a flow rate of 24.0 to 26.0g/min and reacted at a temperature of +2 to-12 ℃ for 13 to 22 s.

Sending the 1, 3-bromochloropropane D phase to a third reaction module by a metering pump at the flow rate of 30.0-40.0 g/min, reacting the 1, 3-bromochloropropane D phase with reaction liquid discharged from the second reaction module at the temperature of + 7-18 ℃ for 6-25 s, and then discharging the reaction liquid to a quenching module;

in the present invention, the following reaction is carried out in the third reaction module:

in this step, if the flow rate of the 1, 3-bromochloropropane D phase is lower than 30.0g/min, the intermediate lithium salt is excessive, which causes waste of raw materials; if the flow rate of the 1, 3-bromochloropropane D phase is higher than 40.0g/min, the 1, 3-bromochloropropane is wasted; accordingly, the flow rate of the 1, 3-bromochloropropane D phase is suitably from 30.0 to 40.0g/min, preferably from 32.0 to 38.0g/min, more preferably from 34.0 to 36.0 g/min;

it is not preferable that the temperature of the reaction carried out in the third reaction module exceeds the range because energy is wasted below 15 ℃. Above 5 ℃, the temperature difference is too large, and the reaction is not stable; preferably, the temperature of the reaction is between +4 and-15 deg.C, more preferably between +2 and-12 deg.C.

Likewise, it is not preferable to conduct the reaction in the third reaction module for a time exceeding the range because the time below 8 seconds is too short to complete the reaction. Above 22s, the time is too long and not necessary; preferably, the reaction time is 8-22 s, and more preferably, the reaction time is 10-19 s.

Preferably, the 1, 3-bromochloropropane D phase is fed into the third reaction module at a flow rate of 32.0-38.0 g/min and reacts for 8-22 s at a temperature of + 4-15 ℃.

More preferably, the 1, 3-bromochloropropane D phase is sent to the third reaction module at a flow rate of 34.0-36.0 g/min and reacts for 10-19 s at a temperature of + 2-12 ℃.

III, feeding the dilute hydrochloric acid E phase into a quenching module by a metering pump at the flow rate of 35.0-50.0 g/min, reacting the dilute hydrochloric acid E phase with a reaction liquid discharged from a third reaction module at the temperature of + 5-10 ℃ for 6-7 s, and carrying out post-treatment to obtain the 5-chloro-2, 2-dimethyl isobutyl valerate.

In the present invention, the following reaction is carried out in the quenching module:

in the step, if the flow rate of the dilute hydrochloric acid phase E is lower than 35.0g/min, quenching is incomplete and needs to be supplemented; if the flow rate of the dilute hydrochloric acid E phase is higher than 50.0g/min, excessive waste is caused; thus, the flow rate of the dilute hydrochloric acid E phase is suitably from 35.0 to 50.0g/min, preferably from 38.0 to 46.0g/min, more preferably from 40.0 to 44.0 g/min;

it is not preferable that the temperature of the quenching reaction in the quenching module exceeds the above range because energy is wasted below 8 ℃. Above 3 ℃, impurities increase; preferably, the temperature of the quenching reaction is between +3 and-8 deg.C, more preferably, the temperature of the reaction is between +1 and-5 deg.C.

Likewise, it is not preferable that the quenching reaction is carried out in the quenching module for a time exceeding the range because the reaction is not completed because the time is too short. The time is too long and not necessary.

In this step, dilute hydrochloric acid E phase is used at a concentration of 0.1 to 2.0N.

Preferably, the molar ratio of the reactants of the phase A, the phase B, the phase C, the phase D and the phase E is 1.0-5.0: 1.0-3.0: 1.0: 1.0-3.0: 1.0 to 5.0.

According to the invention, the main effect of the work-up after the quenching reaction is to extract the product isobutyl 5-chloro-2, 2-dimethylpentanoate.

The post-treatment of the invention is the conventional treatment of water washing, distillation and rectification.

In the present invention, the conventional treatment with water washing is carried out according to the method described in document US 4665226A. The distillation is conventionally carried out according to the method described in document US 4665226A. The rectification is conventionally carried out according to the method described in document US 4665226A.

The product prepared by the method is subjected to mass spectrometry, and the mass spectrometry result is as follows: see figure 2.

FIG. 2 clearly shows the theoretical molecular weight of 243.1128, experimentally determined: 243.1125 is isobutyl 5-chloro-2, 2-dimethylpentanoate

The invention also relates to 5-chloro-2, 2-dimethyl isobutyl valerate prepared by the preparation method, wherein the content of the isobutyl 5-chloro-2, 2-dimethyl valerate is more than or equal to 97.0%.

The yield and purity of the product prepared by the preparation method of the invention are obtained according to the following methods:

calculating the yield of the product by the following calculation formula according to the weight b of the product obtained by the preparation method and the weight a of the feed of isobutyl isobutyrate in a period of time:

(b×144.21)/(a×220.74)×100％

the purity of the product was obtained by conventional gas chromatography.

[ advantageous effects ]

The invention has the beneficial effects that:

according to the invention, metal lithium is replaced by n-butyl lithium, so that the safety risks in the processes of storage, feeding and reaction are reduced;

the invention adopts the continuous flow microchannel reactor, obviously shortens the reaction time from 18 hours to dozens of seconds in the prior art, and greatly improves the reaction efficiency;

compared with the traditional kettle type reaction, the microchannel reaction is more gentle, the content of reaction impurities is low, the purity of the product reaches more than 97%, and the yield reaches more than 91%.

[ description of the drawings ]

FIG. 1 is a process flow diagram for the preparation of isobutyl 5-chloro-2, 2-dimethylpentanoate according to the invention.

FIG. 2 is a diagram of mass spectrometry of the product prepared by the preparation method of the present invention.

[ detailed description ] embodiments

The invention will be better understood from the following examples.

Example 1: preparation of isobutyl 5-chloro-2, 2-dimethylpentanoate

The preparation method comprises the following preparation steps:

I. dissolving diisopropylamine in tetrahydrofuran organic solvent to obtain a diisopropylamine organic solution A phase with the concentration of 25% by weight;

dissolving n-butyllithium in n-hexane to obtain a diisopropylamine n-hexane solution B phase with the concentration of 22% by weight;

pumping the phase A and the phase B into a heat exchange module of the microchannel reactor by a metering pump, and carrying out heat exchange treatment for 5 seconds at the temperature of-27 ℃;

II. Respectively feeding the phase A obtained in the step I and the phase B obtained in the step I into a first reaction module of a microchannel reactor at the flow rates of 80.0g/min and 46.0g/min by a metering pump, reacting for 10s at the temperature of-25 ℃, and discharging the reaction liquid into a second reaction module;

feeding the isobutyl isobutyrate C phase to the second reaction module by a metering pump at a flow rate of 24.0g/min, reacting it with the reaction solution discharged from the first reaction module at a temperature of +2 ℃ for 13s, and then discharging the reaction solution to the third reaction module;

sending the 1, 3-bromochloropropane D phase to a third reaction module by a metering pump at the flow rate of 30.0g/min, reacting the 1, 3-bromochloropropane D phase with reaction liquid discharged from the second reaction module at the temperature of +4 ℃ for 16s, and then discharging the reaction liquid to a quenching module;

III, feeding the dilute hydrochloric acid E phase into a quenching module by a metering pump at the flow rate of 40.0g/min, reacting the dilute hydrochloric acid E phase with a reaction liquid discharged from a third reaction module at the temperature of +1 ℃ for 6s, washing the reaction liquid by water and performing aftertreatment, wherein the obtained product is determined by the detection of the method described in the specification, is an isobutyl 5-chloro-2, 2-dimethylpentanoate product, the yield is 91 percent, and the purity of the product is 97.6 percent.

Example 2: preparation of isobutyl 5-chloro-2, 2-dimethylpentanoate

The preparation method comprises the following preparation steps:

I. dissolving diisopropylamine in an n-hexane organic solvent to obtain a diisopropylamine organic solution A phase with the concentration of 34% by weight;

dissolving n-butyllithium in n-hexane to obtain a diisopropylamine n-hexane solution B phase with the concentration of 19% by weight;

pumping the phase A and the phase B into a heat exchange module of the microchannel reactor by a metering pump, and carrying out heat exchange treatment for 4 seconds at the temperature of-30 ℃;

II. Respectively feeding the phase A obtained in the step I at the flow rate of 170.0g/min and the phase B at the flow rate of 70.0g/min into a first reaction module of a microchannel reactor by a metering pump, reacting the phases at the temperature of +10 ℃ for 26s, and discharging the reaction liquid into a second reaction module;

feeding the isobutyl isobutyrate C phase to the second reaction module by a metering pump at a flow rate of 26.0g/min, reacting with the reaction solution discharged from the first reaction module at a temperature of-12 ℃ for 22s, and then discharging the reaction solution to the third reaction module;

sending the 1, 3-bromochloropropane D phase to a third reaction module by a metering pump at the flow rate of 32.0g/min, reacting the 1, 3-bromochloropropane D phase with a reaction liquid discharged from the second reaction module at the temperature of-15 ℃ for 22s, and then discharging the reaction liquid to a quenching module;

III, feeding the dilute hydrochloric acid E phase into a quenching module by a metering pump at the flow rate of 44.0g/min, reacting the dilute hydrochloric acid E phase with a reaction liquid discharged from a third reaction module at the temperature of minus 5 ℃ for 7s, and carrying out water washing, distillation and rectification post-treatment as described in the specification of the application to obtain a product, wherein the obtained product is detected by the method as described in the specification of the application, the yield is 93 percent, and the purity of the product is 98 percent.

Example 3: preparation of isobutyl 5-chloro-2, 2-dimethylpentanoate

The preparation method comprises the following preparation steps:

I. dissolving diisopropylamine in a cyclohexane organic solvent to obtain a diisopropylamine organic solution A phase with the concentration of 10% by weight;

dissolving n-butyllithium in n-hexane to obtain a diisopropylamine n-hexane solution B phase with the concentration of 15% by weight;

pumping the phase A and the phase B into a heat exchange module of the microchannel reactor by a metering pump, and carrying out heat exchange treatment for 6 seconds at the temperature of minus 10 ℃;

II. Respectively feeding the phase A obtained in the step I and the phase B obtained in the step I into a first reaction module of a microchannel reactor at the flow rates of 50.0g/min and 40.0g/min by a metering pump, reacting for 6s at the temperature of-30 ℃, and discharging the reaction liquid into a second reaction module;

feeding the isobutyl isobutyrate C phase to the second reaction module by a metering pump at a flow rate of 20.0g/min, reacting it with the reaction solution discharged from the first reaction module at a temperature of +8 ℃ for 8s, and then discharging the reaction solution to the third reaction module;

feeding the 1, 3-bromochloropropane D phase into a third reaction module by a metering pump at a flow rate of 34.0g/min, reacting the third reaction module with a reaction liquid discharged from the second reaction module at a temperature of +7 ℃ for 6s, and then discharging the reaction liquid into a quenching module;

III, feeding the dilute hydrochloric acid E phase into a quenching module by a metering pump at the flow rate of 35.0g/min, reacting the dilute hydrochloric acid E phase with a reaction liquid discharged from a third reaction module at the temperature of +5 ℃ for 6s, and carrying out water washing, distillation and rectification post-treatment as described in the specification of the application to obtain a product which is 5-chloro-2, 2-dimethyl isobutyl valerate, wherein the yield is 94% and the purity of the product is 97.8% as determined by detection of the method described in the specification of the application.

Example 4: preparation of isobutyl 5-chloro-2, 2-dimethylpentanoate

The preparation method comprises the following preparation steps:

I. dissolving diisopropylamine in a petroleum ether organic solvent to obtain a diisopropylamine organic solution A phase with the concentration of 18 percent by weight;

dissolving n-butyllithium in n-hexane to obtain a diisopropylamine n-hexane solution B phase with the concentration of 18% by weight;

pumping the phase A and the phase B into a heat exchange module of the microchannel reactor by a metering pump, and carrying out heat exchange treatment for 5 seconds at the temperature of minus 14 ℃;

II. Respectively feeding the phase A obtained in the step I and the phase B obtained in the step I at the flow rates of 200.0g/min and 80.0g/min into a first reaction module of a microchannel reactor by a metering pump, reacting the phases at the temperature of +15 ℃ for 30s, and discharging the reaction liquid into a second reaction module;

feeding isobutyl isobutyrate C phase to the second reaction module by a metering pump at a flow rate of 30.0g/min, reacting it with the reaction solution discharged from the first reaction module at a temperature of-18 ℃ for 30s, and then discharging the reaction solution to the third reaction module;

sending the 1, 3-bromochloropropane D phase to a third reaction module by a metering pump at the flow rate of 36.0g/min, reacting the 1, 3-bromochloropropane D phase with a reaction liquid discharged from the second reaction module at the temperature of-18 ℃ for 25s, and then discharging the reaction liquid to a quenching module;

III, feeding the dilute hydrochloric acid E phase into a quenching module by a metering pump at the flow rate of 38.0g/min, reacting the dilute hydrochloric acid E phase with a reaction liquid discharged from a third reaction module at the temperature of minus 10 ℃ for 7s, and carrying out water washing, distillation and rectification post-treatment as described in the specification of the application to obtain a product which is 5-chloro-2, 2-dimethyl isobutyl valerate, wherein the yield is 92.5% and the purity of the product is 97.3% as determined by detection of the method described in the specification of the application.

Example 5: preparation of isobutyl 5-chloro-2, 2-dimethylpentanoate

The preparation method comprises the following preparation steps:

I. dissolving diisopropylamine in a methyltetrahydrofuran organic solvent to obtain a diisopropylamine organic solution A phase with the concentration of 43 percent by weight;

dissolving n-butyllithium in n-hexane to obtain a diisopropylamine n-hexane solution B phase with the concentration of 20% by weight;

pumping the phase A and the phase B into a heat exchange module of the microchannel reactor by a metering pump, and carrying out heat exchange treatment for 6 seconds at the temperature of minus 19 ℃;

II. Respectively feeding the phase A obtained in the step I at a flow rate of 100.0g/min and the phase B at a flow rate of 50.0g/min into a first reaction module of a microchannel reactor by a metering pump, reacting the phases at the temperature of-20 ℃ for 14s, and discharging the reaction liquid into a second reaction module;

feeding isobutyl isobutyrate C phase to the second reaction module by a metering pump at a flow rate of 22.0g/min, reacting it with the reaction solution discharged from the first reaction module at a temperature of +5 ℃ for 10s, and then discharging the reaction solution to the third reaction module;

sending the 1, 3-bromochloropropane D phase to a third reaction module by a metering pump at the flow rate of 38.0g/min, reacting the 1, 3-bromochloropropane D phase with reaction liquid discharged from the second reaction module at the temperature of +2 ℃ for 10s, and then discharging the reaction liquid into a quenching module;

III, feeding the dilute hydrochloric acid E phase into a quenching module by a metering pump at the flow rate of 46.0g/min, reacting the dilute hydrochloric acid E phase with a reaction liquid discharged from a third reaction module at the temperature of +3 ℃ for 6s, and carrying out water washing, distillation and rectification post-treatment as described in the specification of the application to obtain a product which is 5-chloro-2, 2-dimethyl isobutyl valerate, wherein the yield is 91.9% and the purity of the product is 97.6% as determined by detection of the method described in the specification of the application.

Example 6: preparation of isobutyl 5-chloro-2, 2-dimethylpentanoate

The preparation method comprises the following preparation steps:

I. dissolving diisopropylamine in an organic solvent of n-hexane to obtain a diisopropylamine organic solution A phase with the concentration of 50 percent by weight;

dissolving n-butyllithium in n-hexane to obtain a diisopropylamine n-hexane solution B phase with the concentration of 25% by weight;

pumping the phase A and the phase B into a heat exchange module of the microchannel reactor by a metering pump, and carrying out heat exchange treatment for 5 seconds at the temperature of-23 ℃;

II. Respectively feeding the phase A obtained in the step I and the phase B obtained in the step I into a first reaction module of a microchannel reactor at the flow rates of 150.0g/min and 62.0g/min by a metering pump, reacting the phases at the temperature of +5 ℃ for 20s, and discharging the reaction liquid into a second reaction module;

feeding the isobutyl isobutyrate C phase to the second reaction module by a metering pump at a flow rate of 28.0g/min, reacting it with the reaction solution discharged from the first reaction module at a temperature of-15 ℃ for 26s, and then discharging the reaction solution to the third reaction module;

feeding the 1, 3-bromochloropropane D phase into a third reaction module by a metering pump at the flow rate of 40.0g/min, reacting the third reaction module with the reaction liquid discharged from the second reaction module at the temperature of-12 ℃ for 19s, and then discharging the reaction liquid into a quenching module;

III, feeding the dilute hydrochloric acid E phase into a quenching module by a metering pump at the flow rate of 50.0g/min, reacting the dilute hydrochloric acid E phase with a reaction liquid discharged from a third reaction module at the temperature of minus 8 ℃ for 6s, and carrying out water washing, distillation and rectification post-treatment as described in the specification of the application to obtain a product which is 5-chloro-2, 2-dimethyl isobutyl valerate, wherein the yield is 91.1% and the purity of the product is 97.1% as determined by detection of the method described in the specification of the application.