63 results about "Grignard reaction" patented technology

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.

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 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 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 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 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.

The application relates to the technical field of organic synthesis, and provides a synthesis method of chiral allylamine and application thereof, which takes isoegual and chiral tert-butylsulfonamide as initial raw materials, synthesizes an enamine intermediate M1, adopts a silyl ether protecting group to protect a phenolic hydroxyl group to obtain an intermediate M2, then carries out a Grignard reaction on the intermediate M2 to obtain an intermediate M3, then removes a sulfinyl group from the intermediate M3 to obtain an intermediate M4, and then acetylates to obtain an intermediate M5, and finally removes a silyl ether protecting group from the intermediate M5 to obtain the chiral allylamine. The synthesis method can reduce the preparation cost of the chiral allylamine, is beneficial to industrialized production, optimizes stereoselectivity, and omits a chiral resolution step, and the chiral allylamine can be used for synthesizing colchicine.

The invention is applied to the technical field of medicines, and discloses a synthesis method of a medicine, namely, triphenhydrochlor, for treating Parkinson's disease, which comprises the following steps: S1, taking tetrahydrofuran as a solvent, taking chlorocyclohexane and magnesium powder as raw materials, adding anhydrous lithium chloride as a catalyst, initiating a reaction by using iodine, and performing suction filtration to obtain triphenhydrochlor; preparing a tetrahydrofuran solution of Grignard reagent cyclohexylmagnesium chloride lithium chloride; s2, dissolving propiophenone piperidine hydrochloride in tetrahydrofuran, and slowly dropwise adding into the Grignard reagent obtained in S1 for reaction; and S3, after the reaction is completed, adding diluted hydrochloric acid to terminate the reaction, and separating out the triphenil hydrochloride. According to the synthesis method of the medicine, namely, the triphenhydrochlor hydrochloride, for treating the Parkinson's disease, an anhydrous lithium chloride catalytic system is introduced, so that initiation conditions of a Grignard reaction are remarkably optimized, efficient preparation of a Grignard reagent at normal temperature is realized, the problems of high energy consumption and potential safety hazards caused by a high-temperature reaction in the prior art are avoided, the reaction process is easier to control, and the yield is higher. And the safety of the production process is greatly improved.

The invention provides a preparation method of 1 '-bromospirofluorene xanthene, and relates to the technical field of organic chemical synthesis. 2-phenylbenzoic acid with low price is used as a raw material, and the 1'-bromospirofluorene xanthene with high purity and high yield is obtained through acylation reaction, nucleophilic addition reaction, Grignard reaction, ring closing reaction, demethylation reaction and other reactions.

The invention discloses a preparation method of pentafluorophenyl triethoxy silane, which comprises the following steps: by taking bromopentafluorobenzene and tetraethyl orthosilicate as raw materials, carrying out Grignard reaction under the action of a catalyst to generate pentafluorophenyl triethoxy silane, and carrying out reduced pressure distillation to obtain a pentafluorophenyl triethoxy silane product; the catalyst is magnesium chips, and the Grignard reaction is carried out in an anhydrous organic solvent by taking iodine particles as an initiator; according to the invention, the molar ratio of magnesium chips to bromopentafluorobenzene to tetraethyl orthosilicate to iodine particles is 1: (0.8-1.2): (0.8-1.2): (0.0005-0.001); the magnesium chips and the zeolite are used as a filler layer of the fixed bed reactor, the contact time and the contact area of materials are prolonged, the reaction time is greatly shortened, the purity of the prepared pentafluorophenyltriethoxysilane product can reach 97.0% or above, and the product yield can also reach about 90%.

The utility model belongs to the technical field of chemical production, and particularly relates to a safe Grignard reaction kettle which comprises a reaction kettle body, an initiator feeding pipe penetrates through the left side end of the top of the reaction kettle body, and the input end of the initiator feeding pipe is connected with a flow adjusting mechanism and connected with an initiator storage tank through the flow adjusting mechanism. The initiator storage tank and the flow regulating mechanism are arranged in a flow regulation and control mode, and meanwhile the initiator storage tank is connected with the reaction kettle body through an initiator feeding pipe, the right side end of the top of the reaction kettle body is connected with a magnesium chip feeding mechanism, and a magnesium chip conveying mechanism is arranged on the upper side portion of the magnesium chip feeding mechanism; the magnesium chip conveying mechanism is connected with the reaction kettle body through the magnesium chip feeding mechanism. According to the utility model, the safety problems of overspeed reaction, rapid temperature rise, material flushing and the like caused by improper addition of an initiator are solved, and the stability, the safety and the controllability of the Grignard reaction are ensured.

The application discloses a synthesis method of bifenzhydrylamine intermediate, and relates to the technical field of organic synthesis. The synthesis method comprises the following steps: taking 4-methoxy aniline as a starting material, and obtaining 4-methoxy benzene diazonium salt through a diazotization reaction; decomposing the 4-methoxy benzene diazonium salt to form an aryl free radical, adding a certain amount of benzene to carry out a coupling reaction, and obtaining 4-methoxy biphenyl; then carrying out halogenation reaction on the 4-methoxy biphenyl through a halogenating reagent to obtain 4-methoxy-3-halogen biphenyl; finally, adding a metal amide to carry out nucleophilic substitution, and obtaining 4-methoxy-3-amino biphenyl. The synthesis method of 4-methoxy-3-amino biphenyl provided by the application avoids relatively dangerous and harsh reactions such as nitration reaction and Grignard reaction, the reaction process is relatively safe, raw materials are cheap and easy to obtain, the reaction yield is high, the reaction condition is mild, the synthesis route is short, the equipment investment is small, and the method is easy to industrialize.

The invention belongs to the technical field of chemical synthesis, and particularly relates to a preparation method of methylprednisolone and an intermediate compound thereof. The preparation method comprises the following steps: by taking cortisone as a raw material, carrying out 17 and 21 site upper protecting groups and 3 site upper protecting groups, and carrying out reduction, so as to obtain a methylprednisolone intermediate compound shown as a formula V; and carrying out 5 and 6-site epoxidation, Grignard reaction, 3-site protecting group removal, 4 and 5-site dehydration elimination, 1 and 2-site dehydrogenation and 17 and 21-site protecting group removal on the compound in the formula V to obtain methylprednisolone. The structural formula of the compound of formula V is shown in the specification. The preparation process has the advantages of high yield, high purity, low cost, simplicity in operation and suitability for industrial production.

The invention discloses a synthesis method of a diene liquid crystal monomer, which comprises the following steps: S1, Grignard addition reaction: carrying out Grignard addition reaction on substituted cyclohexyl N-methoxy-N-methyl benzamide and a substituted cyclohexyl methyl chloride Grignard reagent to obtain a ketone intermediate; s2, the ketone intermediate sequentially reacts with 5, 5-dibromobarbituric acid for a bromination reaction, then sodium formate is added into an alcohol solvent for a hydroxylation reaction, then sodium borohydride is added for a reduction reaction, and a vicinal diol intermediate is obtained; and S3, carrying out an orthoformate reaction on the vicinal diol intermediate obtained in the step S2 and triethyl orthoformate in a fluorine-containing alcohol solvent, then heating to reflux, and carrying out an elimination reaction to obtain the target diene liquid crystal monomer. According to the invention, a traditional double bond construction strategy of multiple Wittig reactions is abandoned, a new synthesis route which takes the Grignard reaction as a starting point and finally constructs a diene structure by a one-pot method through a low-temperature orthoformate / elimination reaction carried out in a specific fluorine-containing solvent is designed, the route is simple, the total yield is high, and the overall cost is lower.