167 results about "Grignard reagent" patented technology

The present disclosure provides methods of manufacturing psilocybin and crystalline psilocybin via a reaction of psilocin and tetrabenzylpyrophosphate in the presence of lithium chloride complex Grignard reagent, which is followed by hydrogenation. Methods of producing psilocin from 4-hydroxyindole or 4-acetoxyindole are also provided.

The invention belongs to the technical field of hot melt adhesives, and relates to a damp-heat-resistant bio-based moisture-curing polyurethane hot melt adhesive, which is prepared from bio-based polyol A, bio-based polyether polyol B, an antioxidant, a flatting agent, isocyanate, a coupling agent and an organic amine catalyst. Wherein the bio-based polyol A is prepared by taking itaconic acid and bio-based diol as raw materials, cooperating with a polymerization inhibitor, synthesizing bio-based polyester diol with the number-average molecular weight of 2500-4000 under the action of a second catalyst, and carrying out addition reaction on double bonds on a side chain of the bio-based polyol A and an n-octyl Grignard reagent under the action of a third catalyst, therefore, the bio-based polyol has a long-chain side group. According to the preparation method, itaconic acid and biological dihydric alcohol are used as raw materials to be matched with an n-octyl Grignard reagent to prepare bio-based polyester polyol with a long-chain side group, the bio-based polyester polyol is applied to the moisture-curing polyurethane hot melt adhesive, and the moisture-curing polyurethane hot melt adhesive with excellent moisture and heat resistance is obtained.

The invention discloses a preparation method of an SGLT2 inhibitor key intermediate, and belongs to the technical field of medicinal chemistry. The preparation method comprises the following steps: 1) reacting a compound B with trimethylchlorosilane under an alkaline condition to generate a compound C; 2) reacting the compound C with an aldehyde group reagent on an aromatic ring to generate a compound D; 3) reacting the compound E with a bromination reagent to generate a compound F; 4) preparing the compound F into a Grignard reagent to generate a compound G; 5) carrying out addition reaction on the compound D and a compound G to generate a compound H; and 6) carrying out dehydroxylation and trimethylsilyl protection on the compound H to generate a compound A. According to the preparation method, the risk caused by amplification of the Sandmeyer reaction in the original route is avoided, and meanwhile, the preparation cost of the key intermediate is greatly reduced.

The invention relates to the technical field of preparation of small molecule compound medicines, in particular to a preparation method of (S)-flurbiprofen. The method comprises the following steps: dropwise adding a tetrahydrofuran solution of 4-bromo-2-fluorobiphenyl into a mixture of tetrahydrofuran and magnesium, and reacting to generate a Grignard reagent; mixing tetrahydrofuran, (S)-vinyl chloride oxide and ferric acetylacetonate, dropwise adding the Grignard reagent, performing acidolysis ring opening, and performing methylation with methyl iodide and magnesium iodide to obtain an alpha-hydroxyl aromatic carboxylic acid derivative; and reacting with sodium chlorite, nitroxide free radicals and acetonitrile, and oxidizing to obtain the (S)-flurbiprofen. By introducing a chiral induction unit, effective transmission of chiral information is realized in a coupling stage, an original chiral center is not destroyed in a subsequent reaction, and a product is ensured to have a highly consistent configuration. According to the scheme, the technical problem that a method capable of remarkably improving the optical purity and yield of (S)-flurbiprofen is lacked in the prior art can be solved, and the method has good environmental friendliness and industrial application prospects.

This invention provides a method for synthesizing the anti-AIDS drug enovirine. This invention belongs to the field of pharmaceutical preparation technology. The synthesis method includes the following steps: (1) SM1 compound reacts with Grignard reagent and then reacts with SM2 compound to obtain compound III; (2) Compound III undergoes oxidation reaction to obtain compound II; (3) Compound II undergoes demethylation reaction under the action of demethylation reagent to obtain compound I; (4) Compound I undergoes ethylation reaction to obtain enovirine. The synthesis route of this invention effectively avoids the use of highly toxic cyanide reagents and expensive heavy metal catalysts. At the same time, the reaction conditions of this route are simple and mild, with high yield, and have excellent industrialization prospects.

The invention discloses a preparation method of rosmeltirol, and belongs to the technical field of chemical synthesis. The method comprises the following steps: taking a compound I as an initial raw material, generating a compound II through base catalysis, and performing bromination reaction to obtain a compound III; carrying out Suzuki coupling reaction on the compound III and isopropenyl boronic acid pinacol ester to obtain a compound IV; then reacting with 2, 6-dichloro-4-aminophenol to generate a key intermediate V; performing diazotization coupling reaction to obtain a compound VI, and performing ring closing reaction to form a compound VII; and finally, carrying out hydrogenation reduction to obtain the target product rosimeltirol. The conventional catalyst is adopted to replace a noble metal system, industrial easily-available raw materials are selected to avoid the use of a Grignard reagent, the yield of each step is up to 85% through optimization of reaction conditions, and the purity of a final product reaches 99.8% or above; meanwhile, the raw material cost is reduced, the emission of three wastes is reduced, the operation safety is improved, and a reliable technical scheme is provided for large-scale production of the rosmeltirol.

The utility model relates to a Grignard reagent continuous synthesis device and system, the device comprises a tubular reactor main body and a stirrer, the lower end and the upper end of the reactor main body are respectively provided with a liquid feed port and a discharge port, and the top of the reactor main body is provided with a magnesium powder feeding unit for connection; a jacket for heating and cooling reaction materials is arranged outside the reactor main body; the stirrer comprises a motor and a supporting rod connected with the output end of the motor, the motor is arranged at the top of the reactor main body, the supporting rod extends downwards from the top in the reactor main body, a mixing assembly is arranged on the supporting rod and comprises a push type stirring rod, and holes are distributed in the push type stirring rod. According to the utility model, continuous and efficient mixing of raw materials and magnesium metal and rapid heat transfer and temperature control can be realized, so that the reaction time is greatly shortened; and the flowing process of the materials in the reaction main body is close to a plug flow process, so that the backmixing of the materials is reduced, the radial mixing of the materials is increased, and the product quality of the Grignard reagent is improved.

This invention provides a method for preparing Centhaquine, a drug for treating hemorrhagic shock. Specifically, the preparation method provided by this invention includes the following steps: (S1) providing compound II and compound IV; wherein compound II is prepared by the following method, which includes the steps of: (A) reacting compound I with 1,2-dibromoethane in a first solvent in the presence of base 1 to obtain compound II; and compound IV is prepared by the following method, which includes the steps of: (B) reacting compound III with pinacol diborate in a second solvent in the presence of Grignard reagent to obtain compound IV; (S2) preparation of compound A; and reacting compound II and compound IV in a third solvent in the presence of a catalyst and base 2 to obtain Centhaquine. The preparation method of this invention has a simple and safe synthetic route and operation, readily available raw materials, simple post-processing, high yield, and is suitable for industrial production.

The invention discloses an alpha-aminophosphoryl derivative as well as a preparation method and application thereof. The method comprises the following steps: by taking a quinoline derivative as a raw material and tetrahydrofuran (THF) as a solvent, adding boron trifluoride diethyl etherate in a nitrogen system at the reaction temperature of 0 DEG C, stirring for 15 minutes, reducing the temperature of the reaction system to T1 (-60 DEG C to-30 DEG C), adding a Grignard reagent into the reaction system, and reacting for 30 minutes to obtain a solution A; dissolving a phosphorus reagent in the organic solvent at room temperature in a nitrogen atmosphere to obtain a solution B; and adding the solution A into the solution B, reacting for 6-15 hours at the reaction temperature T2 (0-50 DEG C), and after the reaction is finished, extracting, concentrating and carrying out column chromatography to obtain the target product alpha-aminophosphoryl derivative. The invention provides a novel synthetic route for preparing the alpha-aminophosphonyl derivative, and various phosphorus reagents such as diaryl phosphorus oxide and phosphite ester can be compatible with the reaction. The alpha-aminophosphoryl derivative synthesized by the invention has a good antibacterial effect on gram-positive bacteria, especially staphylococcus aureus.

The invention discloses a preparation method of a cresol trozole trisiloxane intermediate, and belongs to the technical field of fine chemical engineering. The preparation method comprises the following steps: by taking 2, 6-dibromo-4-methylphenol as a raw material, reacting with 3, 4-dihydropyran under the action of p-toluenesulfonic acid, so as to generate an intermediate 2-(2, 6-dibromo-4-methylphenoxy) pyran; reacting with sodium methoxide under the action of a catalyst to generate an intermediate 2-(2-bromo-4-methyl-6-methoxyphenoxy) pyran; then generating a Grignard reagent, carrying out coupling reaction on the Grignard reagent and 3-bromine-2-methallyl, finally reacting with benzotriazole lithium salt, and carrying out acidolysis deprotection to obtain the cresol trozole trisiloxane intermediate. The raw materials are available in the market, the overall yield is high, and a route reference is provided for synthesis of the compounds.

This invention relates to the field of organic synthesis technology, specifically to a highly efficient and stable Grignard preparation and its green preparation method. By weight, it comprises 8-18 parts of a magnesium source, 40-92 parts of a halogenated hydrocarbon, 150-200 parts of a green solvent, 15-20 parts of ethylene glycol dimethyl ether, and 2.3-3.2 parts of a synergistic stabilizer. The green solvent is 2-methyltetrahydrofuran, or a composite solvent with a weight ratio of 2-methyltetrahydrofuran:methyl tert-butyl ether of 150-160:40-50. The synergistic stabilizer is composed of 1.5-2.0 parts of N,N,N',N'-tetramethylethylenediamine and 0.8-1.2 parts of butylated hydroxytoluene, or composed of 1.5-2.0 parts of N,N,N',N'-tetramethylethylenediamine and 1.0 part of phenothiazine. This invention uses a green solvent system to replace traditional toxic and harmful solvents, and combines it with a solvent recovery process to achieve solvent recycling, which greatly reduces waste emissions and makes the production process safer and more environmentally friendly, in line with the development direction of green chemical industry.

The invention discloses a synthesis method of teprenone, which comprises the following steps: dissolving farnesyl acetone in a solvent, and reacting with a Grignard reagent at low temperature to obtain geranyl linalool; the method comprises the following steps: mixing geranyl linalool, alkyl acetoacetate and an organic aluminum catalyst, reacting under a heating condition, adding a dilute acid solution and an organic extraction solvent into the reacted mixed solution, extracting, separating an organic phase to obtain a teprenone crude product, and carrying out reduced pressure distillation purification to obtain teprenone, the yield and the purity of the teprenone in industrial production are improved.

The invention provides a preparation method of pyruvic acid-1-13C, and relates to the technical field of chemical drugs, and the preparation method comprises the following steps: carrying out reaction and post-treatment on 13C-carbon dioxide and a Grignard reagent to obtain pyruvic acid-1-13C; wherein the Grignard reagent comprises a Grignard reagent obtained by reacting magnesium with acetyl halide. The technical problems that in the prior art, a pyruvic acid-1-13C synthesis method has safety risks, raw materials are not easy to obtain, the number of reaction reagent types is large, the number of process steps is large, and the yield is low are solved, the technical effects that safety and environmental protection are achieved, the raw materials are easy to obtain, the process is simple, and the synthesis route is short are achieved, and the obtained pyruvic acid-1-13C is high in purity and high in yield. And clinical test requirements can be met.

Methods for forming a vapor deposition precursor are provided. The method comprises contacting an aluminum halide compound, an alkoxy aluminum compound, and a Grignard reagent to form the vapor deposition precursor. The vapor deposition precursor comprises an dialkyl aluminum alkoxide compound. The vapor deposition precursor is formed without use of a pyrophoric compound. Related compositions, related precursors, and related methods are also provided, among other things.

The invention discloses a synthesis method of a polysubstituted cyclopropyl carbonyl derivative, and belongs to the technical field of organic synthesis and the technical field of medicine synthesis. The method comprises the following steps: (1) taking substituted olefin as a raw material, and obtaining alpha-chlorocyclobutanone through [2 + 2] cycloaddition and reduction reaction; and (2) carrying out rearrangement reaction on the alpha-chlorocyclobutanone and different types of Grignard reagents or organic lithium reagents to obtain the polysubstituted cyclopropyl carbonyl derivative. The synthesis method provided by the invention has the advantages of wide substrate range, good functional group compatibility, mild reaction conditions, no need of preparation of active intermediates or use of expensive transition metal catalysts, simple operation, capability of obtaining various types of cyclopropyl carbonyl compounds, and the like. The practicability of the method is further shown through later-stage functional group modification of complex bioactive molecules and abundant derivatization of polysubstituted cyclopropyl carbonyl products of the complex bioactive molecules.

The method discloses a green synthesis process of acetylene alcohol double Grignard reagent, and the synthesis process comprises the following steps: dissolving benzyl chloride in an organic solvent to prepare solution A, adding metal magnesium to solution A to initiate a reaction, and preparing an initiation reaction solution; (2) dissolving benzyl chloride and acetylene alcohol substances in an organic solvent to prepare solution B; (2) adding solution B in step (2) to the initiation reaction solution in step (1) dropwise to perform a reaction, and preparing acetylene alcohol double Grignard reagent. The application provides a new synthesis method for synthesizing acetylene alcohol double Grignard reagent by using benzyl magnesium chloride, which can avoid a coupling side reaction between benzyl Grignard reagent and benzyl chloride, and does not need excessive metal magnesium.

The embodiment of the present disclosure discloses a kind of azaxanthene fluorescent dyes and preparation method thereof. Among them, azaxanthene fluorescent dyes have the structure shown in general formula (a);The preparation method of azaxanthene fluorescent dyes includes: halogenated benzoic acid and aniline derivative reaction, generate diphenylamine derivative;Diphenylamine derivative is dehydrated and cyclized to generate azaxanthone derivative;The amino group of the azaxanthone derivative is methylated to generate the first nitrogen methyl anthrone derivative;The first nitrogen methyl anthrone derivative is removed from the first protecting group to generate the second nitrogen methyl anthrone derivative;The phenolic hydroxyl group of the second nitrogen methyl anthrone derivative is protected by the second protecting group to obtain the third nitrogen methyl anthrone derivative;The third nitrogen methyl anthrone derivative is reacted with grignard reagent, and the second protecting group is removed under acidic conditions to obtain azaxanthene fluorescent dye.The azaxanthene fluorescent dye can have high luminous efficiency under acidic conditions.

The invention discloses a preparation method of 4-chloromethylstyrene, and belongs to the technical field of synthesis of organic intermediates. 4-bromobenzaldehyde is adopted as a raw material and reacts with ethylene glycol under the action of p-toluenesulfonic acid to generate an intermediate 1; reacting with magnesium metal to generate a Grignard reagent, reacting with acetaldehyde, and hydrolyzing to generate an intermediate 2; finally, under the combined action of methyl dichlorosilane and tri (pentafluorophenyl) boron, the product 4-chloromethyl styrene is generated. The raw materials can be obtained in the market, the reaction of dehydrating benzyl alcohol into olefin and directly chlorinating aldehyde group to generate benzyl chloride is completed by a one-step method under the combined action of methyl dichlorosilane and tris (pentafluorophenyl) boron, the operation is simple and convenient, the overall yield is high, and a route reference is provided for synthesizing the compounds.

The invention provides a synthesis method of an anti-AIDS drug, and belongs to the technical field of drug preparation, the synthesis method comprises the following steps: (1) reacting an SM1 compound with a Grignard reagent, and then reacting with an SM2 compound to obtain a compound shown in a formula III; (2) performing oxidation reaction on the compound in the formula III to obtain a compound in a formula II; (3) performing demethylation reaction on the compound in the formula II under the action of a demethylation reagent to obtain a compound in a formula I; (4) carrying out ethylation reaction on the compound shown in the formula I to obtain enovirin; the synthesis route effectively avoids the use of a highly toxic cyaniding reagent and an expensive heavy metal catalyst, and meanwhile, the route is simple and mild in reaction condition and high in yield, and has an extremely good industrial prospect.

The application provides a preparation method of dihydroxy boron phenylalanine and intermediates thereof. The method comprises the following steps: mixing 4-halogen-Boc-L-phenylalanine of formula (II) with an alkyl borate, and adding a Grignard reagent to obtain an intermediate compound of formula (I): (I) (II).

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 belongs to the technical field of organic chemical synthesis, and particularly relates to a synthetic method of deuterated toluene-D3, which comprises the following steps: reacting deuterated iodomethane with magnesium to obtain a Grignard reagent deuterated methyl magnesium iodide; and then carrying out coupling reaction on the deuterated methyl magnesium iodide and bromobenzene under the catalysis of a nickel metal catalyst to obtain the deuterated toluene-D3. The synthesis method solves the problems of many byproducts, high cost and low utilization rate of deuterated raw materials when the existing toluene synthesis process is used for preparing semideuterated toluene, realizes efficient synthesis of high-purity deuterated toluene-D3, greatly reduces the generation of polymethyl compounds, and is short in production period and simple in post-treatment.

The invention provides a synthesis method of a high-purity hafnium-zirconium metal complex precursor, and belongs to the technical field of high-dielectric-constant materials for super-large-scale integrated circuits. According to the method, hafnium tetrachloride or zirconium tetrachloride is used as a metal source and sequentially reacts with dialkylamine, n-butyllithium and an alkyl magnesium halide Grignard reagent through a one-pot method in a high-purity inert atmosphere, an intermediate does not need to be separated, and a target precursor is obtained after filtration, washing and rectification. The method is simple and convenient in process operation, mild in reaction condition and low in energy consumption; the raw materials are wide in source and low in price, the product yield reaches 82%-88%, and the metal purity is stabilized to be 6N; when the precursor is used for preparing a hafnium oxide / zirconium thin film through atomic layer deposition (ALD), the thickness of the thin film reaches 14.3 nm under 100 cycles, the non-uniformity is smaller than or equal to 0.90%, the requirement of a gate dielectric layer of a super-large-scale integrated circuit for a high-purity and high-efficiency precursor can be met, and the precursor is suitable for industrial amplification production.

The utility model discloses a solid-liquid reactor which is vertically arranged and comprises a reactor barrel and a stirring component arranged in the reactor barrel, an inner cavity of the reactor barrel is divided into an upper buffer cavity and a lower reaction cavity which are communicated with each other, a solid-phase feed port communicated with the upper buffer cavity is formed in the upper part of the outer wall of the reactor barrel, and an overflow discharge port communicated with the upper part of the lower reaction cavity is formed in the middle of the outer wall of the reactor barrel; a liquid phase feeding hole communicated with the lower part of the lower reaction cavity is formed in the lower part of the outer wall of the reactor barrel; the stirring assembly comprises a rotating shaft and a plurality of stirring blades axially arranged at the lower part of the rotating shaft, the upper end of the rotating shaft extends out of the reactor barrel, the stirring blades are arranged in a reaction cavity at the lower part of the reactor barrel, and the uppermost stirring blade is positioned below the overflow discharge hole. When the solid-liquid reactor is used for producing the Grignard reagent, only one-time initiation is needed, subsequent continuous feeding and continuous production are achieved, and the production efficiency is high.

The invention discloses a continuous flow preparation method and a preparation system of a Grignard reagent, and belongs to the technical field of Grignard reagent preparation. The method comprises the following steps: filling magnesium particles with the particle size of 1-10mm in a micro-channel tubular reactor; a halogenated hydrocarbon solution is introduced from the bottom of the microchannel tubular reactor, the Grignard reagent flows out from the top of the microchannel tubular reactor, the retention time of the reaction is 10-45 min, and after the reaction is completed, the Grignard reagent with proper concentration is directly obtained without separating magnesium; the micro-channel tubular reactor is vertically arranged, and filter screens are arranged on a feed port in the bottom and a reaction liquid discharge port in the top of the micro-channel tubular reactor; the magnesium particles are supplemented from the top of the micro-channel tubular reactor. Compared with the prior art, efficiency and safety can be remarkably improved.

The invention relates to the technical field of pesticide intermediates, in particular to a preparation method of a fluralan synthetic intermediate, which comprises the following synthetic route: taking parachloroaniline as an initial raw material, and carrying out acylation reaction on parachloroaniline and pivaloyl chloride in an alkaline solvent to generate a compound 2; performing chlorination reaction on the compound 2 and a chlorinating agent to generate a compound 3; reacting the compound 3 with magnesium in a nitrogen environment to obtain a Grignard reagent intermediate compound 4; reacting the compound 4 with a trifluoroacetic acid derivative to obtain a compound 5; reacting the compound 5 with concentrated hydrochloric acid to obtain a compound 6; generating a compound 7 from the compound 6 under the action of a chlorinating agent; and finally, synthesizing the compound 7 into a compound 8 under the action of a nitrite reagent. The preparation method has the advantages of safe operation, few by-products, mild conditions, easily available raw materials and simple optimization, and is more suitable for industrial large-scale production.

The present disclosure provides processes for preparing alpha-hydroxy esters by adding a vinyl Grignard reagent to an oxalate and thiolizing the resulting double bond. Also provided are alpha-hydroxy esters and synthetic intermediates prepared according to the processes disclosed herein, as well as compositions comprising the alpha-hydroxy esters.

The present disclosure provides methods of manufacturing psilocybin and crystalline psilocybin via a reaction of psilocin and tetrabenzylpyrophosphate in the presence of lithium chloride complex Grignard reagent, which is followed by hydrogenation. Methods of producing psilocin from 4-hydroxyindole or 4-acetoxyindole are also provided.

The invention relates to the technical field of medicines, and provides a synthesis method of a key intermediate of fluralana, which comprises the following steps: S1, carrying out aldol condensation reaction on a compound I and a compound II to obtain a compound III; s2, carrying out ring closing reaction on the compound III and hydroxylamine to obtain a compound IV; s3, the compound IV is subjected to an alkylation reaction under the action of a catalyst aluminum trichloride, and a compound V is obtained; s4, the compound V reacts with a Grignard reagent and then reacts with carbon dioxide, and a compound VI is obtained. Through the technical scheme, the problems of high cost, high impurity content and complex process of the existing synthesis method in the related technology are solved, a good foundation is laid for preparing flurala, and the process is simple to operate, high in conversion rate in each step and suitable for workshop production.

This invention discloses a chiral monophosphine ligand, its preparation method, and its application in asymmetric synthesis. The ligand preparation method involves mixing an N,N',1,2-tetrasubstituted ethane-1,2-diamine compound, phosphorus trichloride, triethylamine, and solvent under a nitrogen or argon atmosphere at -80 to -70°C, and reacting at 60 to 80°C for 6 to 8 hours. The resulting reaction mixture is then cooled to room temperature, and an alcohol, phenol, or Grignard reagent is added dropwise, reacting at 60 to 80°C for 8 to 12 hours. The resulting mixture is then post-treated to obtain the chiral monophosphine ligand. The application involves stirring a nickel catalyst, a chiral monophosphine ligand, a solvent, a diene, and an aldehyde under an argon or nitrogen atmosphere at a specified temperature for 12 to 15 hours. The mixture is then post-treated to obtain the target product. This method utilizes widely available and inexpensive raw materials, and the operation is simple, achieving high stereoselectivity and enantioselectivity in the synthesis of alcohol compounds containing chiral conjugated dienes through a one-step reaction.