21 results about "Methyl chloroformate" patented technology

The invention belongs to the technical field of medicines, and particularly relates to a preparation method of a heart failure treatment drug viriciguat. Specifically, a specific starting raw material is adopted, dimethyl carbonate is used as an acylation reagent, a proper Lewis acid is used for catalysis, and the vericiguat is synthesized under a solvent-free condition. The process avoids the defects of high toxicity, strong corrosivity, difficulty in process condition control, high cost and the like caused by acylation by using methyl chloroformate or dimethyl dicarbonate in the final reaction of the existing Velciguat synthesis process route. The preparation method can be used for preparing high-purity Velciguat with high yield, and the used reagent is low in toxicity, simple and convenient to operate, green, environment-friendly, low in cost and suitable for industrial large-scale production. # imgabs0 #

The invention belongs to the field of organic synthesis, and particularly provides an integrated synthesis method of chlorocarbonyl [4-(trifluoromethoxy) phenyl] methyl carbamate, which comprises the following steps: dropwise adding methyl chloroformate, slowly dropwise adding a NaOH solution, separating liquid, adding the NaOH solution again, azeotropic with water, and realizing integrated synthesis, thereby obtaining the chlorocarbonyl [4-(trifluoromethoxy) phenyl] methyl carbamate. The intermediate [4-(trifluoromethoxy) phenyl] methyl carbamate can be directly used for preparing sodium salt in the next step without discharging, drying and other operations in the synthesis process, and moisture absorption sensitive substances such as sodium hydride, potassium tert-butoxide, sodium methoxide and the like do not need to be used, so that the safety and stability of the synthesis process are improved.

The invention discloses a method for preparing a spirooxindole alkaloid Coerulescine natural product, which comprises the following steps: by taking an o-iodo aniline compound with a chiral sulfinyl prothetic group as a raw material, carrying out coordination induction on chiral sulfinyl as a prothetic group and metal copper, catalyzing a cyclization reaction of amide a-site arylation tandem methyl chloroformate by cuprous iodide, and carrying out condensation reaction on the chiral sulfinyl prothetic group and metal copper to obtain the spirooxindole alkaloid Coerulescine natural product, thereby obtaining the spirooxindole alkaloid Coerulescine natural product. A key aryl quaternary carbon center of a spirooxindole alkaloid Coerulescine natural product is constructed through a cascade reaction catalyzed by one-step cheap metal cuprous iodide, and then the spirooxindole alkaloid Coerulescine natural product is prepared through subsequent chemical conversion. The preparation method provided by the invention is mild in reaction condition and low in energy consumption, cheap metal cuprous iodide is adopted as a catalyst, a tandem cyclization reaction catalyzed by the cheap metal copper in the method is adopted as a key step, and an efficient and universal strategy is developed to synthesize the spirooxindole alkaloid Coerulescine natural product and analogues thereof.

The invention belongs to the field of Velciguat synthesis, and particularly relates to a preparation method of Velciguat and an intermediate product thereof. The preparation method of the Velciguat comprises the following steps: (1) reacting aminomalononitrile with methyl chloroformate to generate an intermediate product I; (2) carrying out ring closing on the intermediate product I and formamidine under an alkaline condition to obtain an intermediate product II; (3) carrying out bromination reaction on the intermediate product II and N-bromosuccinimide to obtain an intermediate product III; (4) reacting the intermediate product III with bis (pinacolato) diboron under the action of a catalyst to obtain an intermediate product IV; and (5) carrying out a reaction on the intermediate product IV and 5-fluoro-1-(2-fluorobenzyl)-3-iodo-1H-pyrazolo [3, 4-b] pyridine to prepare the viriciguat. The method is simple to operate, low in cost and safe in production. The invention also provides the intermediate product obtained by the preparation method.

The invention discloses a synthesis method of high-purity (2S)-(1-tetrahydropyrimidine-2-ketone)-3-methylbutyric acid, and belongs to the field of chemical medicine, and the synthesis method is characterized by comprising the following steps: by taking L-valine methyl ester hydrochloride as a raw material, carrying out condensation, reduction, cyclization and hydrolysis reaction to obtain (2S)-(1-tetrahydropyrimidine-2-ketone)-3-methylbutyric acid; the method has the advantages that the use of highly toxic product methyl chloroformate is avoided, the generation of byproducts is reduced, the product purity is higher, and the method has the effects of lower cost, greenness, environmental protection and easiness in large-scale production.

The present invention relates to the technical field of chemical synthesis, and provides a 4-biphenylmethanol synthesis method, which comprises: S1, uniformly mixing biphenyl, a solvent and a catalyst I, adding methyl chloroformate in an inert atmosphere, and carrying out a reaction to obtain 4-methyl bibenzoate; s2, mixing the methyl 4-bibenzoate, an alcoholic solution and a catalyst II, reacting, and recrystallizing to obtain the 4-biphenylcarbinol, a solution used during recrystallization in S2 comprises ethyl acetate. According to the technical scheme, the problems of low yield and low purity in the synthesis process of 4-biphenylcarbinol in related technologies are solved.

The invention discloses a purification process of hexazinone production wastewater, and relates to the technical field of wastewater treatment. The process comprises the following steps: introducing wastewater of a hexazinone production process into an enamel microfiltration reactor for reaction, and filtering out pretreated wastewater; the pretreated wastewater is pumped into a graphite condensation type oxidation tower, a composite catalyst composed of a sodium methoxide methanol solution and methyl chloroformate is added for a reaction, and oxygenated wastewater is obtained; adjusting the pH value of the wastewater subjected to oxygen catalysis to 7.0-7.5, introducing the wastewater into a biological denitrification reaction tank, and adding a microbial agent compounded by nitrifying bacteria and denitrifying bacteria for reaction to obtain purified wastewater; refluxing 80% of the purified wastewater to a raw material preparation process for hexazinone production for reuse, and discharging the remaining 20% of the purified wastewater after being detected to be qualified; according to the invention, a grading process of pretreatment, catalytic oxidation, biological denitrification and reclaimed water reuse is designed, so that deep purification of high-ammonia-nitrogen COD wastewater is realized.

The invention relates to a green synthesis method of carbendazim. The method comprises the following steps: (1) taking an o-phenylenediamine solution and a cyanamide solution as raw materials, and carrying out condensation cyclization reaction to generate an intermediate 2-aminobenzimidazole; and (2) mixing the 2-aminobenzimidazole obtained in the step (1) with dimethyl carbonate, and carrying out selective methoxycarbonylation reaction in the presence of a basic catalyst to obtain a reaction product containing carbendazim. According to the method, a biodegradable green reagent dimethyl carbonate is adopted to replace highly toxic methyl chloroformate and upstream phosgene which are required to be used in a traditional process, so that the green, safe and environment-friendly process is guaranteed from the source.

The application belongs to the field of vixepiromide synthesis, and particularly relates to a preparation method of vixepiromide and intermediate products thereof. The preparation method of vixepiromide comprises the following steps: (1) reacting aminopropandinitrile with methyl chloroformate to generate an intermediate product one; (2) ring closing the intermediate product one with formamidine under alkaline conditions to generate an intermediate product two; (3) performing bromination on the intermediate product two with N-bromosuccinimide to generate an intermediate product three; (4) reacting the intermediate product three with pinacol diboron under the action of a catalyst to generate an intermediate product four; and (5) reacting the intermediate product four with 5-fluoro-1-(2-fluorobenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridine to generate vixepiromide. The application has the advantages of simple operation, low cost and safe production. The application further provides the intermediate products generated in the above preparation method.

The production process comprises the following steps: S1, placing cyanamide into a reaction container, and adding a solvent and a phase transfer catalyst into the reaction container; s2, raising the temperature to a reaction temperature, adding methyl chloroformate while stirring, and keeping the reaction temperature for reaction after the methyl chloroformate is added; and S3, after the reaction is finished, cooling to separate out crystals, dissolving the crystals in a hydrochloric acid solution, extracting, and distilling to obtain the cyanamide methyl formate. And the phase transfer catalyst is adopted, so that sufficient contact of cyanamide salts and methyl cyanamide formate with different polarities during reaction is facilitated, the reaction is promoted, the reaction yield is improved, and the method has a wide application prospect.

The invention belongs to the technical field of photovoltaic materials, and particularly relates to an organic-inorganic composite polymer ultraviolet cut-off agent, a preparation method and a packaging adhesive film, and the preparation method comprises the following steps: heating cyanuric chloride, resorcinol, a Lewis acid catalyst and a solvent 1, 2-dichloroethane for reaction to obtain a solid compound I; dropwise adding acryloyl chloride into the compound I, triethylamine and tetrahydrofuran at low temperature, and precipitating to obtain a solid compound II; the compound II, methyl chloroformate, sodium bicarbonate and methylbenzene are subjected to a heating reflux reaction, and a compound III is obtained; heating the compound III, N, N-dimethylformamide and potassium carbonate, and dropwise adding bromo-isooctane to obtain a compound IV; the compound IV, polyethylene glycol 400, methanesulfonic acid and a toluene solution are subjected to a heating reflux reaction, and a compound V is obtained; the compound V, MTMP, KH-571, a toluene solution and an initiator are subjected to a heating reaction, and a compound VI is obtained; dissolving the compound VI and titanic acid in dichloromethane, adding HCl, dopamine hydrochloride and H2O2, and mixing to obtain a compound VII;

The invention discloses an analysis method for precolumn derivatization of a hydrogenation impurity of a melogabalin besylate intermediate, the melogabalin besylate intermediate is MB-2, and the hydrogenation impurity in the melogabalin besylate intermediate is MB-2A, the analysis method comprises the following steps: (1) using a derivatization reagent to perform precolumn derivatization on the melogabalin besylate intermediate; carrying out derivative reaction on the melogabalin besylate intermediate under the catalysis of alkali to obtain derivative reaction liquid; the derivatization reagent is o-phthalaldehyde, fluorenyl methyl chloroformate or 2, 4-dinitrofluorobenzene; and (2) detecting the derivative reaction liquid by using a high performance liquid chromatography-UV detector to obtain the content of the hydrogenated impurities in the melogabalin besylate intermediate. According to the analysis method, the content of MB-2A in MB-2 can be effectively separated and accurately quantified, the accuracy is high, the detection line is low, and the method is high in durability. # imgabs0 #

The invention discloses methyl cyanamide synthesis technique, belongs to the field of pharmaceutical synthesis technology, synthesis technique, comprises the following steps:By grafted carrier, toluene, methacryloylpropyl dimethyl benzyl ammonium chloride and azobisisobutyronitrile mixing, under nitrogen protection condition, 80 DEG C of stirring reactions 7 8h, after reaction terminates, through filtration, vacuum drying, obtain supported catalyst;Cyanamide is diluted with water, methyl chloroformate is subsequently added, and it is regulated that reaction system pH value is 9 11, adds supported phase-transfer catalyst, and setting temperature is 45 50 DEG C, stirring reaction, obtains methyl cyanamide.The process flow of the present invention is simple, by the control of reaction conditions and the operation such as adding supported phase-transfer catalyst in technique, improve reaction efficiency, reduce the generation of by-products, improve product purity.

This invention relates to a method for the efficient preparation of methyl cyanurate, belonging to the technical field of pharmaceutical intermediate synthesis. The method includes the following steps: mixing 1-hydroxyethyl-3-methylimidazolium acetate with a 28-32% potassium phosphate aqueous solution at a mass ratio of (2.8-3.2):1, followed by allowing the mixture to stand and separate into upper and lower phases; adding a cyanamide aqueous solution to the lower phase; and continuously adding methyl cyanurate to the upper phase; stirring the reaction at 40-50°C for 1.5-2.5 hours; allowing the mixture to stand and separate into upper organic and lower brine phases; diluting the upper organic phase with 1.8-2.2 times its volume of deionized water, precipitating a solid, followed by filtration; collecting the filter cake and filtrate; washing and drying the filter cake to obtain methyl cyanurate. This invention achieves directional distribution of reactants, precise suppression of side reactions, and efficient separation of products by constructing a two-phase aqueous system.

The application belongs to the technical field of heterocyclic compounds, and particularly relates to a preparation method of arecoline and a preparation method of a base material of a betel quid. 1,2,5,6-tetrahydropyridine and formic acid are dissolved in water, an aqueous formaldehyde solution is added after being heated, and then the mixture is kept warm, the pH is adjusted, and an organic layer is extracted. The organic layer is spin-dried to obtain N-methyl tetrahydropyridine. The N-methyl tetrahydropyridine is dissolved in N,N-dimethylacetamide, a palladium catalyst, a palladium catalyst ligand and an organic base catalyst are added, and then the mixture is heated after being replaced by nitrogen. Methyl chloroformate is added under the protection of nitrogen to react, and then the mixture is cooled and filtered to obtain a filtrate. Methyl sulfonic acid is added to the filtrate to react, and then the mixture is cooled and filtered to obtain arecoline methanesulfonate. The arecoline methanesulfonate is added to water, the pH is adjusted, and then the mixture is extracted. The obtained organic layer is concentrated to obtain arecoline crude product, and then the arecoline crude product is subjected to negative pressure rectification to obtain pure arecoline. The process flow is greatly simplified, the production conversion is facilitated, the yield of the prepared arecoline is high, and the purity of the prepared arecoline is high.

The invention discloses a thiophanate-methyl synthesis method, and relates to the technical field of pesticide synthesis, and the thiophanate-methyl synthesis method comprises the following steps: S1, dissolving sodium thiocyanate in water, adding a catalyst, adding methyl chloroformate, and after the reaction is finished, carrying out liquid separation to obtain methyl isothiocyano formate; s2, methyl isothiocyano formate is added into 1, 2-dichloroethane, and a methyl isothiocyano formate solution is obtained; the preparation method comprises the following steps: adding o-phenylenediamine into 1, 2-dichloroethane, stirring and dissolving, dropwise adding into a methyl isothiocyano formate solution, keeping the temperature to react for 30-60 minutes, cooling and crystallizing, thereby obtaining the o-phenylenediamine methyl isothiocyano formate. The catalyst comprises modified dialkylaniline; the modified dialkylaniline comprises magnesium lithium silicate serving as a carrier, and further comprises dialkylaniline. The thiophanate-methyl synthesized by the method provided by the invention has high yield and content.

The invention belongs to the technical field of heterocyclic compounds, and particularly relates to a preparation method of arecoline, a buccal bag base material and a preparation method of the buccal bag base material. The preparation method comprises the following steps: dissolving 1, 2, 5, 6-tetrahydropyridine and formic acid in water, heating, adding a formaldehyde aqueous solution, keeping the temperature, adjusting the pH value, extracting to obtain an organic layer, and spin-drying the organic layer to obtain N-methyltetrahydropyridine; the preparation method comprises the following steps: dissolving N-methyltetrahydropyridine in N, N-dimethylacetamide, adding a palladium catalyst, a palladium catalyst ligand and an organic base catalyst, heating after nitrogen replacement, adding methyl chloroformate under the protection of nitrogen for reaction, cooling and filtering to obtain filtrate; adding methanesulfonic acid into the filtrate for reaction, cooling and filtering to obtain arecoline mesylate; the method comprises the following steps: adding arecoline mesylate into water, adjusting the pH value, extracting, concentrating the obtained organic layer to obtain a crude arecoline product, and carrying out negative pressure rectification to obtain a pure arecoline product. According to the method, the technological process is greatly simplified, production conversion is facilitated, and the prepared arecoline is high in yield and purity.

The invention relates to the technical field of pesticide synthesis, and discloses a continuous synthesis method of thiophanate-methyl. The method comprises the following steps: preparing dry sodium thiocyanate into an aqueous solution, and continuously reacting with methyl chloroformate and a catalyst in a microreactor; and carrying out condensation reaction on the obtained intermediate and o-phenylenediamine dissolved in the composite solvent in series connection stirring kettles, and carrying out programmed cooling and crystal growing, separation, washing and drying to obtain the product. According to the method, side reaction is effectively inhibited, the product purity is high, the quality is stable, the production efficiency and the reaction yield are remarkably improved, and the microreactor and the reaction kettle are connected in series to realize whole-process continuous operation; by using the self-made efficient catalyst, the dosage of the catalyst is reduced, the reaction condition is mild, the reaction temperature is effectively reduced, the process time is shortened, meanwhile, the catalyst has no peculiar smell, the problem of irritating odor is avoided, and the operation environment is friendly.

The invention relates to a preparation method of methyl trifluoroethyl carbonate. The preparation method comprises the following steps: (1) carrying out a reaction on di-tert-butyl dicarbonate and trifluoroethanol to obtain an intermediate product; (2) adding dimethyl carbonate into the reaction system in the step (1), and reacting to obtain methyl trifluoroethyl carbonate; the reaction in the step (1) is carried out in the presence of a catalyst. The preparation method has the advantages of few reaction steps and high selectivity and yield. Compared with the existing synthesis method, the synthesis raw material is di-tert-butyl dicarbonate, high-toxicity raw materials such as methyl chloroformate are avoided, and the method is green and environment-friendly. And methanol which can generate ternary azeotropy with the product FEC and the dimethyl carbonate during rectification is not generated in a reaction system, so that the product purity is improved. In addition, the reaction product carbon dioxide in the step (2) escapes, the reaction is promoted to proceed forwards, and the reaction yield is increased.

According to the device and the method for continuously synthesizing the methyl chloroformate, the device for continuously synthesizing the methyl chloroformate synthesizes the methyl chloroformate by using a series device of the supergravity reactor and the micro-channel reactor, and the series device can realize extremely high phosgene utilization rate. The supergravity reactor can enable the raw materials methanol and phosgene to be mixed more uniformly in a microscopic state, so that the raw materials methanol and phosgene can react more sufficiently to generate methyl chloroformate, and formation of dimethyl carbonate by-products is reduced. Reaction liquid generated in the supergravity reactor and pre-reaction tail gas can be continuously introduced into the micro-channel reactor to be mixed, so that unreacted phosgene and methanol can be continuously reacted to generate methyl chloroformate, the residual quantity of a methanol raw material in a product is reduced, and reaction liquid with high content of methyl chloroformate is obtained. By using the device, the synthesis efficiency and yield of the methyl chloroformate are greatly improved, the use amount of phosgene can be further reduced, and the green chemistry concept is met.

The invention discloses a solid-liquid separation process for producing carbendazim, and belongs to the field of pesticide production. The solid-liquid separation process comprises the following process steps: preparing carbendazim through a methyl chloroformate synthesis method to obtain an original feed liquid, performing primary membrane separation, mixing an ethanol water solution, performing secondary membrane separation, recovering and drying to obtain a carbendazim solid. A two-time membrane separation method is adopted for classified screening, primary membrane separation can quickly separate most of carbendazim crystals with conventional sizes in original feed liquid, large-particle-size crystals are prevented from blocking tiny pores of secondary membrane separation, then the carbendazim crystals are blended with an ethanol water solution, the solubility of organic impurities is improved, and the separation efficiency is improved. The method comprises the following steps of: separating crystals by using a membrane, effectively stripping impurities on the surfaces of the crystals, deeply washing the crystals, finally separating by using a secondary membrane, intercepting submicron fine crystals, deeply intercepting the microcrystals in a targeted manner, effectively adsorbing and removing the impurities, and improving the yield and the purity of products.