88 results about "Grignard reaction" patented technology

The invention relates to a synthesis process of p-chlorophenylboronic acid, which comprises the following steps: by taking tetrahydrofuran as a solvent and p-dichlorobenzene as an initial raw material, firstly preparing p-chlorophenylmagnesium chloride through Grignard reaction, then reacting the p-chlorophenylmagnesium chloride with boric acid ester in a microchannel reactor to obtain a p-chlorophenylboronic acid ester crude product, and then hydrolyzing, layering and carrying out oil-phase azeotropic distillation to obtain the p-chlorophenylboronic acid ester. And finally, recrystallizing by adopting a mixed system of an alcohol solvent and a benzene solvent to obtain p-chlorophenylboronic acid with the content of 98% or above. The synthetic process of the p-chlorophenylboronic acid is mild in reaction condition, simple and convenient to operate, low in cost, high in safety, high in product content and very suitable for being applied to industrial large-scale production.

The invention relates to the technical field of organic synthesis, in particular to a method for constructing Orforglipron tetrahydropyran ring chirality through enzyme catalysis, which comprises the following steps: step S1, taking SM1 as a raw material, and carrying out hydrolysis resolution in a solvent, a buffer salt system and enzyme catalysis to obtain a chiral pure intermediate INT-1; step S2; performing ring closing on the INT-1 through Grignard reaction to synthesize a lactone intermediate; s3, carrying out Diball-H reduction, quenching, dichloromethane extraction and anhydrous sodium sulfate drying on the INT-4, and then reducing the INT-4 by using triethyl silane to obtain an intermediate INT3; step S4, coupling the INT-3 in the presence of a catalyst and a ligand to obtain an intermediate INT-4; step S5, carrying out deprotection and salification on the INT-4 to obtain an intermediate INT5; s6, closing an indole ring from INT5 to obtain a compound of which the general formula is A; chirality is constructed through enzyme catalysis, isomer impurities do not need to be split and separated through SFC when the chirality is constructed, the loss is reduced, the yield is increased, and a target product is obtained with high chiral selectivity; meanwhile, the cost is relatively reduced, and the cost is saved.

The present invention relates to the technical field of organic synthesis, and specifically relates to a method for constructing the chirality of a pyran ring in Orforglipron by means of enzymatic catalysis, the method comprising the following steps: step S1, by using SM1 and SM2 as starting materials, carrying out a reaction under the action of a palladium catalyst and a ligand to obtain INT-1; step S2, under the catalysis of Pd / C, subjecting INT-1 to double bond hydrogenation reduction to obtain INT-2; step S3, in the presence of a solvent, a buffer salt system and enzymatic catalysis, subjecting INT-2 to hydrolysis and resolution to obtain a chirally pure intermediate INT-3; step S4, subjecting INT-3 to a Grignard reaction for cyclization, so as to synthesize a lactone intermediate INT-4; and step S5, subjecting INT-4 to reduction by means of Dibal-H, quenching same, performing extraction with dichloromethane, drying same with anhydrous sodium sulfate, and then performing reduction by means of triethylsilane to obtain a compound of general formula A. In the present invention, the chirality is constructed by means of enzymatic catalysis without the need of SFC resolution for separating isomeric impurities during the construction of the chirality, thereby reducing losses and improving yield, obtaining the target product at high yield and high chiral selectivity, and further saving expenses and reducing costs.

The invention relates to the field of chemistry or medicinal chemistry, in particular to a synthesis method of isoxazoline anti-parasitic drug lotirasodium. The synthesis method comprises the following steps: firstly, synthesizing an intermediate 1 (1, 2, 3-trichloro-5-(1-trifluoromethyl-vinyl) benzene); then synthesizing an intermediate 2 (5-bromo-4-methyl-2-thiophenecarboxime); the preparation method comprises the following steps: carrying out a 1, 3 dipolar cycloaddition reaction on an intermediate 1 and an intermediate 2 in sequence to obtain an intermediate 3, carrying out a Grignard reaction to obtain racemic acid, and finally carrying out chemical resolution and amide condensation in sequence to obtain lotirasodium. According to the novel synthesis method of the isoxazoline anti-parasitic drug lotirazine, wittig reaction is adopted for the first time to obtain the intermediate 1, operation is simpler and more convenient, and reaction conditions are mild. Besides, the synthesis method of the intermediate 2 is improved, so that the reaction conditions are milder, the operation is simpler, the cost is greatly reduced on the basis of reported reaction conditions, and the method is suitable for industrialization.

The present invention discloses a preparation process of Grignard alcohol, which uses magnesium and methyl chloride as reaction raw materials, tetrahydrofuran as a solvent, and iodine crystals as an initiator. The Grignard reaction is carried out under nitrogen to generate a Grignard reagent, and then the Grignard reagent reacts with p-chlorobenzophenone by an addition reaction to generate Grignard alcohol. The magnesium includes pre-treated magnesium powder and magnesium strips. By simultaneously using magnesium powder and magnesium strips with specific mass ratios and size ratios and pre-treating them, the present invention can ensure the stable progress of the reaction and improve the reaction yield; in addition, by carrying out the treatment of removing water and peroxides from tetrahydrofuran, while ensuring the process safety, the yield of the Grignard alcohol product can be further improved.

This invention discloses a method for synthesizing a venetum intermediate, specifically as follows: Step 1: In an organic solvent, 2,4-difluorobenzoic acid and 5-hydroxy-7-azaindole undergo an etherification reaction under the action of an acid-binding agent. After the reaction, post-treatment yields 2-((1h-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-fluorobenzoic acid; Step 2: 2-((1h-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-fluorobenzoic acid reacts with 1-((2-(4-chlorophenyl)-4,4-dimethylcyclohexene-1-)methyl)piperazine in… An amination reaction occurs under the action of a base. After the reaction, post-treatment yields 2-(7-azaindole-5-oxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohexene-1-)methyl)piperazine-1-)benzoic acid, i.e., Venetantora intermediate III. The synthetic process provided by this invention avoids Grignard reactions and subsequent hydrolysis reactions, shortens the operation steps, simplifies the synthetic process, and provides a simple and easy-to-operate synthetic process. The raw materials are inexpensive and readily available, while avoiding the use of highly toxic raw materials. The production process is green and environmentally friendly, and suitable for industrial production.

The invention discloses a preparation method of 4-chloro-2-fluoro-3-methoxyphenylboronic acid and a preparation method of the 4-chloro-2-fluoro-3-methoxyphenylboronic acid. The specific implementation process comprises the following steps: by taking 1-bromo-4-chloro-2-fluoro-3-methoxybenzene as a raw material, carrying out Grignard reaction on magnesium chips and an initiator in an organic solvent to synthesize 4-chloro-2-fluoro-3-methoxyphenyl magnesium bromide; and the 4-chloro-2-fluoro-3-methoxyphenyl magnesium bromide and boric acid ester are synthesized into the 4-chloro-2-fluoro-3-methoxyphenylboronic acid, and then the 4-chloro-2-fluoro-3-methoxyphenyl magnesium bromide and boric acid ester are synthesized into the 4-chloro-2-fluoro-3-methoxyphenylboronic acid. The novel synthesis method of 4-chloro-2-fluoro-3-methoxyphenylboronic acid is designed, the total synthesis yield of the method ranges from 88% to 95%, compared with an existing synthesis route, the problems that a traditional route relates to an ultralow temperature condition and strong alkali, is low in safety and high in cost are solved, and the method has the advantages of being simple, environmentally friendly, safe, efficient and the like and is suitable for industrial production. Meanwhile, the method has a relatively good industrialization prospect.

The invention belongs to the technical field of drying equipment for Grignard reaction, and particularly relates to an automatic moisture drying system and method for benzenetetrasolvent in maltol production, and the system comprises a pre-drying storage tank, a first-stage drying storage tank, a first-stage circulating pump and a first-stage drying tower; the bottom of the before-drying storage tank is connected with an upper inlet of a first-stage drying storage tank through a pipeline, a bottom outlet of the first-stage drying storage tank is connected with a first-stage circulating pump, an outlet of the first-stage circulating pump is connected with an upper inlet of a first-stage drying tower, and an outlet of the first-stage drying tower is connected with the upper inlet of the first-stage drying storage tank; an outlet of the first-stage circulating pump is connected with an upper inlet of the second-stage drying storage tank, an outlet of the second-stage drying storage tank is connected with an inlet of the second-stage circulating pump, an outlet of the second-stage circulating pump is connected with an upper inlet of the second-stage drying tower, and a lower outlet of the second-stage drying tower is connected with an upper inlet of the second-stage drying storage tank. According to the invention, the benzene tetrasolvent is automatically dried in maltol production, and manual operation is not needed.

The invention relates to the technical field of medical and chemical medicines, in particular to a novel synthesis method of L (-)-threo-3-hydroxyaspartic acid hydrochloride. The preparation method comprises the following steps: by taking cheap and easily available D-phenylglycinol as an initial raw material, firstly protecting amino with Boc anhydride, then oxidizing to obtain N-BOC-D-phenylalanine aldehyde 3, then carrying out Grignard reaction on the N-BOC-D-phenylalanine aldehyde 3 and vinyl magnesium bromide at low temperature to obtain corresponding o-amino alcohol, then reacting the o-amino alcohol with 2, 2-dimethoxypropane at 0 DEG C under the catalytic action of p-toluenesulfonic acid, and finally obtaining the 2, 2-dimethoxypropane. The obtained compound 4 is subjected to Upjohn dihydroxylation reaction and sodium periodate oxidation to obtain corresponding aldehyde, and then the aldehyde is oxidized by potassium permanganate under a weak acidic condition to obtain corresponding carboxylic acid 5. Oxidizing a benzene ring by taking ruthenium trichloride as a catalyst and sodium periodate as a co-oxidant to obtain dicarboxylic acid; and finally, refluxing and deprotecting by using hydrochloric acid to obtain the L (-)-chloro-3-hydroxyaspartic acid hydrochloride.

The invention provides a novel method for preparing an intermediate compound of aromatic sesquiterpenes Commiphoranes C-D. The method comprises the following steps: substituting the ortho-position of a compound 1 with iodine through n-butyllithium and diiodoethane to obtain a compound 2; removing methoxyl by using boron tribromide to obtain a compound 3; performing nucleophilic substitution on 3-allyl bromide and potassium carbonate to synthesize a compound 4; carrying out Grignard reaction to obtain a compound 5; oxidizing into a compound 6 through a Dess-Martin oxidizing agent; finally, (CH3Si) 3SiH and triethyl boron are subjected to intramolecular free radical series cyclization, so that synthesis of an aromatic sesquiterpene Commiphoranes C-D intermediate compound is successfully completed, sufficient preparation is made for follow-up total synthesis of the natural product, key intramolecular free radical series cyclization has the capacity of efficiently constructing a polycyclic system, and the synthesis process is simple and convenient. According to the preparation method, the defects of expensive reagents, long 14-step linear synthesis route, low yield and the like in the existing synthesis route are overcome; the popularization potential is high.

The utility model provides continuous reaction equipment for preparing sartan biphenyl and belongs to the technical field of reaction equipment. Comprising a support frame; the Grignard reaction cabin is stably mounted on the supporting frame and is used for carrying out a preparation reaction of a Grignard reagent; the coupling reaction cabin is stably mounted on the support frame and is used for carrying out coupling reaction to generate the sartan biphenyl; and the cooling part is stably mounted on the supporting frame. Through cooperation of the Grignard reaction cabin, the coupling reaction cabin and the cooling part, the temperature requirement of the coupling reaction is met under the condition of not additionally arranging heating equipment, the energy consumption and the cost are reduced, and meanwhile through structural cooperation of a pressure relief opening formed in one side of the gas storage cabin, an internal sealing plug, a spring and a plurality of gas inlet channels, the pressure relief opening is formed in the other side of the gas storage cabin. And the pressure can be automatically relieved when the air pressure in the air storage bin is too high.

The invention provides a continuous production method and device of diphenyldimethoxysilane. The method comprises the following steps: 1) continuously adding a fresh first solvent, halogenated benzene, a fresh second solvent a and magnesium chips into a Grignard reactor at the same time, and carrying out Grignard reaction to generate a Grignard reagent; 2) continuously overflowing the Grignard reagent into a substitution reactor, and mixing the Grignard reagent with a continuously pumped fresh monomer and a fresh second solvent b for substitution reaction to obtain a substitution reaction solution; 3) filtering the substitution reaction liquid, and continuously rinsing the filter cake with a fresh second solvent c to obtain a wet filter cake, filtrate and rinsing liquid; 4) drying and dehumidifying the rinsed wet filter cake under reduced pressure to obtain a liquid-phase material flow and magnesium salt; (5) continuously feeding the filtrate and the rinsing liquid in the step (3) and the liquid-phase material in the step (4) into a solvent distillation system, and distilling to obtain a crude product, a circulating first solvent, a circulating monomer and a circulating second solvent; recycling the circulating first solvent, the circulating monomer and the circulating second solvent; and 6) product distillation.

The invention discloses a high-yield synthesis method of elxalidone, and relates to the technical field of drug synthesis. 1-chloro-2-(trifluoromethyl) benzene and 4-(methylsulfonyl) aniline are used as initial raw materials; according to the present invention, the isaprorenone is obtained through the Grignard reaction, the addition reaction, the bromination reaction, the condensation reaction, the substitution reaction, the cyclization reaction, the reduction reaction, the substitution reaction and the chiral resolution, and the synthesis method has advantages of low raw material cost, short route, high yield and the like, and can be used for the quantitative production of the isaprorenone.

The application discloses a synthesis method of flurbiprofen and an intermediate thereof. The intermediate of the flurbiprofen is 3-fluoro-4-biphenyl boronic pinacol ester, and the synthesis method comprises the following steps: step A: 2-fluoro-4-bromobiphenyl is subjected to a coupling reaction with bispinacolyl diboron under the action of an alkali and a metal catalyst to obtain 3-fluoro-4-biphenyl boronic pinacol ester. The synthesis method of the flurbiprofen comprises the following steps: step C: 3-fluoro-4-biphenyl boronic pinacol ester is subjected to a coupling reaction with sodium 2-bromopropionate under the action of an alkali and a metal catalyst, and then the obtained reaction product is acidified to obtain flurbiprofen. According to the application, 2-fluoro-4-bromobiphenyl is prepared into 3-fluoro-4-biphenyl boronic pinacol ester, and then the 3-fluoro-4-biphenyl boronic pinacol ester is subjected to a Suzuki coupling reaction with sodium 2-bromopropionate to prepare flurbiprofen, the method has less side reactions, and the molar yield is high, which is obviously higher than the yield in the literature of preparing flurbiprofen by means of Grignard reaction.

The application provides a preparation method of 2,4,6-trifluorobenzoic acid, which comprises the following steps: 1) subjecting 1,3,5-trifluorobenzene to a bromination reaction to obtain 2,4,6-trifluorobromobenzene; and 2) subjecting the 2,4,6-trifluorobromobenzene to a Grignard reaction to obtain 2,4,6-trifluorobenzoic acid. The method has the advantages of short flow, simple process, high molar yield and high purity of 2,4,6-trifluorobromobenzene, low cost of 2,4,6-trifluorobenzoic acid prepared by the method, and relatively environmentally-friendly and safe operation process, and is suitable for large-scale production.

The invention relates to a synthetic method of 2-diphenylmethyl pyrrolidine or an acid salt of 2-diphenylmethyl pyrrolidine. In order to solve the problems of easy ring opening and low yield in the prior art, the invention provides a synthetic method of 2-diphenylmethyl pyrrolidine or an acid salt thereof, which comprises the following steps: in the presence of an alkaline reagent, performing amidation and esterification reaction on a compound pyrrole-2-formic acid as shown in a formula II and ethyl chloroformate in an ROH solvent to obtain a compound as shown in a formula III; r in the ROH solvent is alkyl; performing Grignard reaction with phenyl magnesium bromide to obtain a compound as shown in a formula IV; carrying out reduction reaction on the compound shown in the formula IV under the catalytic action of trifluoroacetic acid and triethyl silane to obtain a compound shown in a formula V; and carrying out hydrolysis reaction on the compound in the formula V under an alkaline condition to obtain the compound 2-diphenylmethylpyrrolidine in the formula I or the acid salt thereof. According to the method, ring-opening impurities can be effectively avoided, the yield is increased to 95% or above, and the purity reaches 99% or above.

The utility model discloses a special reaction kettle for Grignard reaction, and relates to the field of fine chemical engineering. The reaction kettle special for the Grignard reaction comprises a reaction kettle body, a stirring assembly used for stirring a solution is installed in the reaction kettle body, and the reaction kettle further comprises a separation disc which is fixedly connected into the reaction kettle body and located below the stirring assembly; the hollow filter column is rotationally connected to the center position of the bottom of the separation disc through a fixing rod; according to the reaction kettle, the separation disc, the water spraying pipe, the hollow filter column, the blade plate group, the circulating pump, the liquid pumping pipe and the liquid conveying pipe are matched for use, so that when the reaction kettle is used for Grignard reaction, excessive magnesium chips can be intercepted in the reaction kettle and can be continuously used by a reaction solution in the next reaction; and the residual magnesium chips can be prevented from blocking filter holes of the filter assembly to influence the flow speed of the solution, so that the smoothness of discharging the solution out of the reaction kettle is effectively ensured.

The invention relates to a uniform feeding device of a Grignard reaction kettle, which comprises a feeding ring, a fixed ring and a rotating part, the fixed ring is arranged in the reaction kettle, the feeding ring is rotatably mounted on the fixed ring, the feeding ring is provided with a ring groove, the bottom of the feeding ring is provided with a plurality of feeding holes, and the fixed ring is provided with a feeding pipe connected with an external feeding pump. One end of the feeding pipe is communicated with the annular groove, a stirring assembly is arranged in the reaction kettle, and the rotating part is arranged in the reaction kettle and connected with the stirring assembly; before reaction, a base solution is added into the reaction kettle, the feeding pump feeds materials into the annular groove of the feeding ring through the feeding pipe, the materials are discharged through the feeding hole in the bottom of the feeding ring, meanwhile, the stirring assembly stirs the materials, and the rotating part drives the feeding ring to rotate and discharge the materials for dropwise adding reaction. And low yield caused by overhigh local reaction concentration is not easy to occur.

The utility model relates to a solvent recovery device for Grignard reaction. The solvent recovery device comprises a tank body, a water inlet is formed in the tank body, a filter plate is arranged in the tank body, a filter screen is installed on the filter plate, a cover plate is arranged at an opening in the top of the tank body, a lifting mechanism is arranged on the tank body, the cover plate is connected with the filter plate, and a blow-off pipe is arranged on the lower side of the tank body. A water outlet pipe and an oil outlet pipe are arranged on the side wall of the tank body; when the filter screen on the filter plate is used for a period of time and needs to be cleaned, the lifting mechanism drives the cover plate to further drive the filter plate to move, so that the filter screen on the filter plate can be cleaned, and the filter screen on the filter plate can be cleaned. The filter screen is detached from the filter plate at the opening of the tank body for replacement, the lifting mechanism sends the filter plate back into the tank body, and the device has the effect that the filter plate is convenient to detach and replace.

This invention discloses a method for preparing tetraenestrol, comprising the following steps: S1. Etherification reaction: In a solvent and in the presence of a catalyst, compound I is etherified with methanol to generate compound II, yielding a solution of compound II; S2. Grignard reaction: The solution of compound II obtained in S1 is reacted with a Grignard reagent to generate compound III, yielding a solution of compound III; S3. Hydrolysis reaction: In the presence of an acid, the solution of compound III obtained in S2 is hydrolyzed to generate compound IV, yielding a solution of compound IV; S4. Dehydrogenation reaction: In the presence of a dehydrogenation reagent, the solution of compound IV obtained in S3 is dehydrogenated to generate compound V, yielding tetraenestrol. This preparation route features simple reaction operation, high overall yield, and high product purity, reducing the overall production cost.

The application belongs to the technical field of liquid crystal materials, and relates to a trans-decahydronaphthalene indole liquid crystal compound and a preparation method thereof. The application provides a trans-decahydronaphthalene indole liquid crystal compound, which has a chemical structural formula as shown in formula (I). The preparation of the compound of formula (I) comprises the following steps: obtaining a compound of formula (III) from a compound of formula (II) through a Grignard reaction, oxidizing the compound of formula (III) to obtain a compound of formula (IV), and obtaining the compound of formula (I) from the compound of formula (IV) through a Fischer indole synthesis reaction. The preparation method is simple in operation, high in product yield and purity, and the prepared trans-decahydronaphthalene indole liquid crystal compound can be applied to special liquid crystal materials.

The application discloses a modified polysilane-polysiloxane body type crosslinking copolymer scintillator and a preparation method thereof. The crosslinking copolymer scintillator is a body type crosslinking structure formed by crosslinking of modified polymethylhydrosilane and polymethylphenylsiloxane. In the application, a scintillation group with 2-3 aromatic rings is introduced into a Si-Si main chain through a Grignard reaction, so that an original sigma conjugated system is expanded into a sigma-pi and sigma-pi conjugated system. Correspondingly, introduced pi electrons and lone pair electrons (n electrons) are converted into pi to sigma transition and pi to n to sigma transition, so that the energy gap width is changed, and the fluorescence emission spectrum of the polysilane becomes adjustable. After modification, the conjugated system is expanded, and the intermolecular electron transfer is improved, so that the fluorescence intensity and the quantum yield of the polysilane are improved. The fluorescence intensity of the modified scintillation group is 20-40 times higher than that of the unmodified polysilane-polysiloxane crosslinking copolymer.

A method for synthesizing the tomato leafminer sex pheromone (3E,8Z)-3,8-tetradecadienyl acetate. The present invention uses 3-butyn-1-alcohol as a starting material, and obtains a target fragment A through hydroxyl protection, Grignard reaction, reduction and acetylation; the protected 3-butyn-1-alcohol is subjected to bromination reaction, cross-coupling reaction of alkynyl bromide and Grignard reagent, reduction, deprotection and halogenation to obtain a target fragment B; the Grignard reagents of target fragments A and B undergo a Grignard reagent coupling reaction under the catalysis of Li2CuCl4 to obtain a key intermediate. Finally, the target product, tomato leafminer sex pheromone (3E,8Z)-3,8-tetradecadienyl acetate, is obtained through deprotection and acetylation. The raw materials of the present invention are cheap and easily available, all reaction conditions are mild, it is easy to scale up, there is little pollution to the environment, and promotion has good economic and social value.

This invention provides a method for preparing squalene. The method involves reacting 1,4-dihalobutane and magnesium powder via a Grignard reaction to obtain the corresponding Grignard reagent, which is then reacted with 5-chloro-2-pentanone via an addition reaction and acidification to prepare 1,12-dichloro-4,9-dimethyldodecyl-4,8-diene. The obtained 1,12-dichloro-4,9-dimethyldodecyl-4,8-diene and magnesium powder are then reacted with the Grignard reagent to obtain the corresponding Grignard reagent, which is then reacted with 6-methyl-5-hepten-2-one via an addition reaction and acidification to prepare squalene. The raw materials used in this invention are inexpensive and readily available. Only two Grignard and addition reactions are required to obtain the target product, making the steps simple. The reaction conditions are mild, the equipment is simple, the cost is low, and it is easy to industrialize. Wastewater generation is low, making it green, safe, and environmentally friendly. The reaction has high selectivity, few byproducts, and high yield and purity of the target product, making it suitable for green industrial production.

The invention relates to the technical field of organic synthesis, and particularly discloses a preparation method of 4-isopropenylphenol, which comprises the following steps: hydroxyl protection: under the action of stirring, adding p-hydroxyacetophenone or p-hydroxybenzaldehyde into a solvent A, then adding a hydroxyl protective agent and alkaline ion exchange resin, carrying out heat preservation reaction at 10-15 DEG C for 3-4 hours, filtering, washing, and drying to obtain 4-isopropenylphenol; filtering, extracting and concentrating to obtain an intermediate 1; grignard reaction: under the stirring action, adding the intermediate 1 into a solvent B, heating to 35-45 DEG C, then dropwise adding a Grignard reagent, continuously carrying out heat preservation reaction for 5-6 hours, after the reaction is finished, adding a hydrochloric acid solution, standing for phase separation, and concentrating to obtain an intermediate 2; the Grignard reagent is isopropyl magnesium chloride or methyl magnesium chloride. According to the preparation method provided by the invention, the 4-isopropenylphenol with the yield being greater than or equal to 60% and the purity being greater than or equal to 98% can be obtained, the reaction operation is simple, and large-scale industrial production is facilitated.

The invention provides a method for preparing 2, 4, 6-tri (4 '-butoxy-2'-hydroxyphenyl)-triazine, which comprises the following steps: in the presence of an alkaline reagent, dissolving m-bromophenol and n-butyl bromide in a first solvent to carry out nucleophilic substitution reaction, and after the reaction is finished, carrying out post-treatment to obtain 1-bromo-3-butoxybenzene; magnesium chips and an initiator are dissolved in a second solvent for a reaction, then the 1-bromo-3-butoxybenzene is dropwise added for a Grignard reaction, and a 3-butoxybenzene Grignard reagent is obtained; dropwise adding boric acid ester into the 3-butoxybenzene Grignard reagent for reaction, and then adding an oxidizing agent for oxidation reaction to obtain 3-butoxyphenol; 3-butoxyphenol and cyanuric chloride are dissolved in a third solvent for a reaction, lewis acid is added for a Friedel-Crafts reaction, after the reaction is finished, aftertreatment is conducted, and the 2, 4, 6-tri (4 '-butoxy-2'-hydroxyphenyl)-triazine is obtained.The preparation method is lower in cost, higher in yield, high in product quality and easy to control.

The invention discloses a preparation method of vinyl liquid polycarbosilane, which comprises the following steps: preparing a vinyl Grignard reagent through a multi-step Grignard reaction, and reacting with polycarbosilane to construct a vinyl-containing polycarbosilane molecular structure, thereby effectively enhancing the ceramic yield of liquid polycarbosilane and the performance of a subsequent SiC ceramic-based composite material.

The invention discloses a method for continuously preparing 4-fluoro-2-trifluoromethyl acetophenone, which comprises the following steps of: pre-filling a magnesium metal bed layer in a Grignard reactor, respectively feeding a 2-bromine-5-fluorobenzotrifluoride solution and magnesium metal from the bottom and the top of the Grignard reactor, introducing inert gas from the bottom of the Grignard reactor, and continuously reacting at the temperature of between 20 and 30 DEG C to obtain 4-fluoro-2-trifluoromethyl acetophenone. After being distributed by the microporous disperser, the gas uniformly enters the Grignard reactor from bottom to top, and the gas discharged from a gas outlet in the top of the Grignard reactor is re-introduced into the bottom of the Grignard reactor; reaction liquid obtained after the Grignard reaction is completed flows out and then is divided into two parts, a small part of the first part returns to the bottom of the Grignard reactor to serve as an initiator of the Grignard reaction, and a large part of the second part is sequentially subjected to acylation reaction and acidolysis reaction and then is subjected to post-treatment, so that the target product 4-fluoro-2-trifluoromethyl acetophenone is obtained. The method has the advantages of high reaction efficiency, simple system, low cost and the like, and industrial production is easy to realize.

The invention relates to the technical field of organic synthesis industrialization, in particular to a novel synthesis method of a canagliflozin key intermediate, which comprises the following steps: by taking 2-halothiophene as a starting material, carrying out Grignard reaction and coupling to obtain 2-(4-fluorophenyl) thiophene. The route has the advantages that the cost is controllable, the industrialization of reaction conditions is easy to realize, the quality of the obtained product is greatly improved, and the market competitiveness is stronger.

The invention relates to a (S)-3-halo-5-substituted pyridine derivative and an asymmetric catalytic synthesis method thereof.The compound has a specific chiral center structure and can be used as an important medical intermediate, and the preparation process adopts three-step continuous reaction: firstly, performing Grignard reaction under a low-temperature condition to construct an acetyl framework; then, high-selectivity asymmetric reduction is realized by using a ruthenium catalyst with a specific configuration; and finally, carrying out mild methylation reaction to obtain a target product. By optimizing the catalyst system, the reaction temperature and the material ratio, the optical purity and the reaction yield of the product are remarkably improved, and meanwhile, the common side reaction problem in the traditional process is avoided. The method is easy and convenient to operate, mild in condition and suitable for industrial production, and an efficient and reliable synthesis path is provided for preparation of chiral drug intermediates.