119 results about "Salt formation" patented technology

A preparation equipment and a process for a nylon salt solution. The preparation equipment includes a suspension preparation device, a first salt formation reactor and a second salt formation reactor. The suspension preparation device includes a feeding unit, a continuous feeding unit, a high-shear pump and a mixing reactor, the high-shear pump and the mixing reactor are cyclically connected with and in communication with each other through two connecting pipelines; the second salt formation reactor includes a second diamine feed pipe, a third diamine feed pipe, a circulation pipeline of the second salt formation reactor and an online near-infrared monitoring equipment located on the circulation pipeline of the second salt formation reactor.

The invention discloses a preparation method of 3-quinuclidinone hydrochloride, which comprises the following steps: carrying out temperature control reaction on 4-picolinic acid and chloroacetic acid under alkaline water conditions to obtain an aqueous solution of a compound a, and directly entering the next reaction without post-treatment after the reaction is finished; adding a reducing agent alkaline water system into the aqueous solution of the compound a, controlling the temperature to react, controlling the temperature to adjust the pH value to 5-5.5 after the reaction is finished, extracting with n-butyl alcohol, and drying to obtain an n-butyl alcohol solution of a compound b, and directly entering the next reaction step; wherein the reducing agent is one of sodium borohydride and potassium borohydride; dropwise adding thionyl chloride into an n-butyl alcohol solution of the compound b, controlling the temperature to react after dropwise adding is ended, and concentrating to remove the solvent and unreacted thionyl chloride after the reaction is ended, so as to obtain a compound c; carrying out Dieckmann condensation reaction on the compound c at controlled temperature under the condition of organic alkali by using toluene as a solvent, carrying out hydrochloric acid quenching reaction after the reaction is finished, and directly carrying out next-step reaction after extracting and removing impurities from a water phase containing a hydrochloride solution of a compound d by using toluene; and carrying out a decarboxylation reaction on the compound d in a hydrochloric acid aqueous solution at controlled temperature, after the reaction is finished, adjusting the pH value to 10-13, extracting, and salifying to obtain a target compound TM, namely 3-quinuclidinone hydrochloride. The preparation method of 3-quinuclidinone hydrochloride provided by the invention has the advantages of economical and easily available raw materials, mild reaction conditions, efficient reaction, simple operation and low cost, and is suitable for industrial application.

The present invention provides a method for separating and purifying mevastatin from a mevastatin mother liquor. The method primarily comprises the steps of gradient hydrolysis ring-opening and salt formation, stripping and impurity removal, extraction and purification, and condensation ring-closure. The gradient hydrolysis ring-opening step controls the generation of impurities, and this, combined with the stripping and impurity removal step, synergistically improves the yield and purity of mevastatin. The mevastatin separation and purification method provided by the present invention ultimately yields mevastatin with a purity exceeding 90% and a yield exceeding 80%.

The application belongs to the technical field of pharmaceutical chemistry synthesis, and specifically discloses a preparation method of oseltamivir and a phosphate thereof and an intermediate thereof, which comprises the following steps: (1) a compound of formula VII is reacted with VIII under the action of a base in a solvent to obtain an intermediate of formula VI, and then the intermediate of formula VI is reacted under the action of a strong base at high temperature to obtain formula V; (2) formula V is subjected to ring-opening reaction with tert-butylamine in a solvent under the catalysis of a Lewis acid to obtain formula IV; (3) formula IV is reacted with an acetylating agent in a solvent under the action of a base to obtain formula III; (4) formula III is reacted under the action of an acid at a certain temperature to obtain formula II; and (5) formula II is subjected to salt formation with phosphoric acid in a solvent to obtain oseltamivir. The preparation method has the characteristics of simple operation, low cost, high yield, high optical purity of the product, stable process and the like, and is suitable for industrial production.

This invention relates to the field of pharmaceutical technology and discloses a method for improving the clarity and color of oxybuprocaine hydrochloride solution, comprising the following steps: S110: Oxoplasmin is added to a reactor, and an organic solvent is added while stirring to control the reaction system at 0-10°C; an antioxidant is added. S120: Hydrochloric acid is slowly added in batches to the temperature-controlled reaction system. After the addition is complete, the temperature is controlled at 0-10°C for 2-4 hours, then the temperature is raised to 40-50°C for 2-4 hours, and activated carbon is added. S130: The mixture is filtered while hot, and solvent is slowly added dropwise to the filtrate until the product precipitates. After slurrying at 25-35°C for 2 hours, the mixture is filtered, and the filter cake is vacuum dried in a vacuum drying oven at 40-50°C for 12-16 hours to obtain oxybuprocaine hydrochloride. This invention provides a novel method for obtaining oxybuprocaine hydrochloride by adding antioxidants and activated carbon in the salt formation step. The clarity and color of the resulting product solution meet pharmacopoeia requirements.

The application discloses a synthesis method of 3,3-difluorocyclopentylamine hydrochloride, and particularly relates to the technical field of chemical synthesis. The synthesis method comprises the following steps: taking 2-cyclopentenone and phthalimide as raw materials, and sequentially performing a Michael addition reaction, deoxygenation fluorination, removal of a phthaloyl protecting group, Boc protection and deprotection and salt formation reaction to obtain 3,3-difluorocyclopentylamine hydrochloride. The synthesis route and process design of the application are reasonable, the starting raw material is 2-cyclopentenone, the required reaction condition is mild, the post-treatment method is simple, the operability is strong, the raw material and reagent are cheap and easy to obtain, and the total yield can reach 43.6%, so the synthesis method has large-scale preparation value.

This invention relates to the field of chemical process technology, specifically to a method for preparing sodium hexafluoroantimonate. The preparation method includes the following steps: (1) adding antimony trioxide, hydrogen fluoride aqueous solution, and sodium fluoride into a reaction vessel, stirring and heating, introducing a fluorine-nitrogen mixed gas, and then refluxing the reaction; (2) filtering and then flash evaporation concentration; (3) subsequently cooling and crystallizing at 0~15℃, and centrifuging to obtain sodium hexafluoroantimonate crystals. The preparation method provided by this invention can achieve fluorination, oxidation, and salt formation in one step simultaneously, with a simple process route and a significant reduction in steps; using low-concentration fluorine gas as an oxidant and fluorine source, the atom utilization rate is high, the reaction rate is fast, the raw material consumption is close to the stoichiometric ratio, the final product has a trivalent antimony residue of ≤0.01%, and the product purity is as high as 99.9%; combined with flash evaporation concentration, hydrogen fluoride and mother liquor recovery and recycling process, it can reduce raw material consumption and waste liquid discharge, thereby improving product yield and reducing production costs.

The invention relates to the technical field of organic synthesis, in particular to a refining method of a crude product of dextroborneol, which comprises the following steps: sequentially carrying out a rearrangement reaction, an esterification reaction, a salt forming reaction, an alkaline hydrolysis reaction and post-treatment refining on the crude product of dextroborneol in the presence of a solvent and a catalyst on the basis of a reaction product to obtain a refined product of dextroborneol, in the refined dextroborneol product, the content of dextroborneol is greater than or equal to 98.0%, the content of L-borneol is less than or equal to 1.0%, the content of isoborneol is less than or equal to 0.15%, the content of natural camphor is less than or equal to 0.15%, and the content of other impurities is less than or equal to 0.10%. The method has the advantages that the isoborneol structure can be selectively destroyed under mild conditions, impurities are effectively removed through the esterification-salification-alkaline hydrolysis three-step reaction, and the purity and yield of dextroborneol are remarkably improved.

The invention belongs to the field of medicinal chemistry, and particularly relates to a preparation method of a lutrombopag intermediate, which comprises the step of preparing an intermediate I p-toluenesulfonate by using a new salifying system.

The application discloses a preparation method of a trans-7H-pyrrolo[2,3-d]pyrimidine compound, and the full name of the trans-7H-pyrrolo[2,3-d]pyrimidine compound is trans-N-methyl-4-(methyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)cyclohexylmethanesulfonamide maleate, which is prepared from trans-4-[(tert-butoxycarbonyl)amino]cyclohexane carboxylic acid and 4-chloro-7H-pyrrolo[2,3-d]pyrimidine as starting materials through reduction, chlorination, substitution, oxidation, methylation, condensation and salt formation reactions. The preparation method has the advantages of few reaction steps, simple operation, low production cost, high production efficiency, high yield, high product purity and suitability for scale-up production.

A method for resolving a phenylalanine derivative of formula (I), and an intermediate. The method comprises: a resolving step comprising using a resolving reagent to react with the phenylalanine derivative represented by formula (I) in a reaction solvent to obtain a resolved intermediate, wherein the resolving reagent is selected from N-acetyl-D-phenylalanine and / or (2R,3R)-(−)-dibenzoyl-L-tartaric acid, and the reaction solvent is selected from 90-99% aqueous ethanol, absolute ethyl alcohol, or acetone. The method uses a chiral reagent to perform salt formation and racemate resolution, and has the advantages of being easy to operate, requiring no special production devices, and being easy to scale up production.

The present invention discloses a preparation method and application of an oxime ester photoinitiator having a donor-acceptor structure. The preparation method constructs a large conjugated donor-acceptor structure oxime ester photoinitiator with triphenylamine as a donor, pyridinium salt as an acceptor, and oxime ester as a photoinitiator group through reactions such as Suzuki coupling, hydroxylation, oxime esterification, and salt formation. The photoinitiator can be used in photocuring systems such as coatings, inks, and 3D printing. It has high photoinitiation efficiency under both visible light and sunlight, and can meet the requirements of deep curing in different complex environments. The photoinitiator has the advantages of high initiation efficiency, ultra-low addition amount, and deep curing depth. The preparation process is simple, the raw materials are easily available, and large-scale industrial production can be achieved.

The present invention belongs to the technical field of agricultural herbicides and relates to a thiopyralid intermediate compound, a preparation method and an application thereof. The thiopyralid intermediate compound is shown in structural formula (I) and is a stable compound that can be conveniently crystallized, separated, purified, stored and transported. The three-step reaction for preparing the thiopyralid intermediate compound (I) has a stable yield and mild reaction conditions, thereby improving the safety of the process. In addition, in the reaction of synthesizing thiopyralid (II) from the intermediate compound (I) of the present invention, the reaction conditions of the diazotization hydrolysis and salt formation steps are mild, and the yield can reach more than 90%.

The application provides a kind of solvent-free salt formation reaction equipment and process, shell is provided with feed inlet, feed inlet is connected with the grinding chamber in the shell feed, temperature control sleeve is arranged outside the grinding chamber, and the reaction cabin capable of overturning is arranged in the grinding chamber;Ultrasonic tool head is arranged on the grinding chamber above the reaction cabin, the top cover of the reaction cabin can be opened and closed, and the bottom cover of the reaction cabin is hollow fiber reverse osmosis membrane.The process of the application is simple, the combination device can effectively eliminate the influence of raw material residues, the water is removed quickly and completely, the reaction time is short, the energy consumption is low, the content of the obtained product is high, the impurities are few, and a new idea is provided for the synthesis of related products of such raw materials.

The invention provides a preparation method and application of a ziprasidone related substance B, and belongs to the technical field of heterocyclic compound synthesis. Ziprasidone is taken as an object, ziprasidone is salified to synthesize ziprasidone mesylate, ziprasidone mesylate is dissolved and dispersed in a solvent containing activated carbon, after 5-7 days of standing, the solvent is filtered and concentrated, and a related substance B is obtained through crystallization. When the scheme is applied to crystallization of ziprasidone salt, generation of a related substance B can be effectively inhibited, and the product quality is improved.

The application discloses a preparation method of high-purity fluorescein sodium. The fluorescein is synthesized from o-phthalic anhydride and resorcinol under the catalysis of sodium bisulfate or potassium bisulfate without using an organic solvent as a solvent, and then the fluorescein is used to prepare fluorescein diacetate; and the high-purity fluorescein sodium is obtained through a synthesis route of saponification, acidification and salt formation. The synthesis route has mild reaction conditions, simple operation steps, no organic solvent, avoids the generation of organic solvent pollution, has low raw material and auxiliary material consumption, low production cost, high purity of reactants and high yield.

This invention relates to a method for preparing trinitromethyl tricyclic compounds containing nitrogen-rich groups, belonging to the field of energetic materials technology. The specific preparation steps are as follows: Scheme 1 uses 2,3-diaminomaleonitrile to obtain the corresponding methyl ester-substituted intermediate through multiple steps of cyclization, acidification, and esterification. Then, through multiple steps of hydrazine substitution, cyclization with ethyl 3-ethoxy-3-iminopropionate hydrochloride, ester hydrolysis, and nitration, the target compound trinitromethyl tricyclic compound 2 is successfully synthesized. Scheme 2 uses ethyl diazonium acetate to obtain the corresponding methyl ester-substituted intermediate through multiple steps of cyclization, acidification, and esterification. Then, through multiple steps of hydrazine substitution, cyclization with ethyl 3-ethoxy-3-iminopropionate hydrochloride, nitration, salt formation, and renitration, the target compounds trinitromethyl tricyclic compounds 1, 3, and 4 are synthesized. The target compound has advantages such as high nitrogen content, high density, good thermal stability and excellent detonation performance, and can be used as a component of energetic materials, showing potential application value.

This invention discloses a method for synthesizing an intermediate of retinoic acid, relating to the field of pharmaceutical organic synthesis technology, comprising the following steps: S1, in the presence of a base, 2-amino-3-chloropyridine and 4-bromopiperidine undergo a nucleophilic substitution reaction in solvent A to prepare compound III; S2, in the presence of a catalyst and ammonia solution, compound III undergoes an amination reaction in solvent B to prepare compound II; S3, compound II is dissolved in solvent C, and sequentially undergoes CDI cyclization and hydrogen chloride solution salt formation to prepare compound I, namely 1-(piperidin-4-yl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one. This invention is low-cost, uses mild reaction conditions, has a simple synthesis process, high yield, and eliminates the need for expensive and potentially unsafe excipients, effectively improving reaction safety, being environmentally friendly, and suitable for industrial production.

The invention discloses a synthesis method of an FLT3 inhibitor of quinatinib dihydrochloride. According to the method disclosed by the invention, the raw material drug of the quinatinib dihydrochloride is synthesized and prepared through seven chemical reactions including Boc protecting group feeding, bromination reaction, condensation ring closing reaction, Boc protecting group removal, phosgene condensation reaction, final etherification reaction to obtain the quinatinib, and final salification. The method has the advantages of wide raw material source, low cost, simplicity in operation, high product recovery rate, easiness in industrial industrialization and the like.

The present invention relates to the field of medical intermediates, and provides a preparation method for a key intermediate tert-butyl (3aR,5S,6aS)-5-(methylamino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate mesylate of a JAK kinase inhibitor. The method comprises: reacting tert-butyl cis-5-oxohexahydrocyclopenta[C]pyrrole-2(1H)-carboxylate as a raw material with a methylamine equivalent to obtain intermediate A; and then carrying out a reduction reaction in metallic sodium and isopropanol to obtain a crude product, adding L-DBTA to form a salt, removing isomers, and then carrying out re-liberation and salt formation with methanesulfonic acid to obtain a purified product. The method significantly reduces reaction steps, reduces raw material costs, has a simple and reliable process, and is easy for industrial production.

The present invention provides a production method suitable for industrial production of (2S,3S)-3-amino-2-(3-bromo-2-fluorobenzyl)pyrrolidine having a protecting group at the 1-position.The present invention is a method for producing N-[(4-methylphenyl)sulfonyl]-L-phenylalanine salt of (2S,3S)-3-amino-2-(3-bromo-2-fluorobenzyl)pyrrolidine having a protecting group at the 1-position, which comprisesStep 2: a step of subjecting 2-(3-bromo-2-fluorobenzyl)-3-(methoxyimino)pyrrolidine having a protecting group at the 1-position to a reduction reaction; andStep 3: a step of subjecting the product obtained in Step 2 to optical resolution using salt formation with N-[(4-methylphenyl)sulfonyl]-L-phenylalanine.

The application relates to the technical field of permanent ferrite preparation, in particular to a method for preparing strontium ferrite by a multi-field coupling auxiliary molten salt method. First, a chemical coprecipitation method is improved to obtain a mixture containing an excess precipitant, inorganic salt and strontium ferrite precursor; then the mixture is subjected to heat treatment under multi-field coupling; finally, strontium ferrite powder is obtained after washing and drying. The application simplifies the chemical coprecipitation process, avoids Sr loss and realizes in-situ salt formation; a multi-element molten salt system is constructed during heat treatment, and an alkali-containing molten salt system with activation is proposed; in the molten salt liquid phase environment, multi-physical fields such as magnetic fields and ultrasonic vibration force fields are cooperated to control the orientation and growth of grains, new driving force and fast channels are provided for ion diffusion, and the rapid synthesis of strontium ferrite and the control of microstructure and size are realized in a low temperature and short time.

This invention relates to the field of materials technology, and more particularly to a 3D-printed, internally hollowed-cone solar interface evaporator with directional salt deposition function, its preparation method, and its application. The invention includes step 1: three-dimensional model construction; step 2: substrate surface pretreatment and chemical activation; and step 3: hydrothermal preparation of a Co-Bi-S coating. This invention uses a 3D-printed porous, internally hollowed-cone resin device as a substrate, and grows a Co-Bi-S coating in situ on its surface using a hydrothermal method. This coating exhibits both excellent photothermal conversion performance and corrosion resistance. The evaporator structure is designed as a porous, internally hollowed-cone shape, which provides a larger evaporation area, stronger light capture and focusing capabilities, and can achieve higher evaporation temperatures and directional salt deposition effects. The prepared solar interface evaporator exhibits excellent photothermal conversion performance and water evaporation efficiency, and also demonstrates good structural stability and corrosion resistance. This solves the technical problems of low photothermal conversion efficiency and poor stability in high-salt environments inherent in traditional solar evaporators, making it suitable for applications such as seawater desalination.

The invention discloses an industrial preparation method of a photochromic material common intermediate, and belongs to the technical field of organic synthesis. Performing deacetylation on the mixture 3A / 3B to generate a mixture 4A / 4B, then adding organic alkali to complex into salt, filtering to remove solids, and treating filtrate to obtain a compound 4A; adding alkali and hydrolyzing to obtain a compound 5; and finally, carrying out ring closing reaction to generate a product C. The invention creatively develops a simple and novel method for removing impurities by salifying, avoids the column chromatography of the traditional process, greatly improves the production efficiency, saves the cost, and improves the market competitiveness of the product.

This invention provides a method for preparing labetalol hydrochloride, belonging to the field of pharmaceutical synthesis. The method uses 5-acetylsalicylic acid as a starting material, obtains 3-bromo-5-(2-bromoacetyl)-2-hydroxybenzamide through bromination, then undergoes a substitution reaction with 1-methyl-3-phenylpropylamine, followed by hydrogenation reduction, and finally salt formation to obtain labetalol hydrochloride. The method provides a high conversion rate and few byproducts by using the synthesized 3-bromo-5-(2-bromoacetyl)-2-hydroxybenzamide intermediate to replace 5-bromoacetylsalicylic acid. The obtained product can be directly used in the next reaction, followed by substitution and reduction to obtain the final product. This method is low-cost, high-yield, simple, and controllable, facilitating industrialized production and showing excellent application prospects.

The application discloses a long carbon chain polyamide continuous salting method and system, and the method comprises the following steps: mixing a long carbon chain binary acid dispersion liquid I and a long carbon chain binary amine dispersion liquid II in a mixer, and then feeding the mixture into a reaction kettle to obtain a reaction product; the reaction product is divided into two streams, a first stream of the reaction product is circulated back into the reaction kettle, and a second stream of the reaction product is taken out. In the method, the conversion rate of the reaction kettle binary acid is greater than 99.50%, the particle size of the obtained solid salt particles is located in the range of 20-40 microns, the particle size distribution is narrow, and the impurity content in the solid salt is less than 0.20 wt%.

The invention relates to the technical field of chemical synthesis of nucleic acid, and discloses a purification method for protecting uridine and modified uridine DMTr, which comprises the following steps: dissolving or suspending a substrate in a reaction solvent, adding a set amount of alkaline reagent, controlling the temperature, adding a set equivalent amount of 4, 4 '-dimethoxytriphenylmethyl chloride, completing the reaction at the set temperature, and after the reaction is completed, separating and purifying to obtain the uridine and modified uridine DMTr. Carrying out post-treatment: quenching the reaction liquid, and carrying out liquid-liquid extraction on the reaction system after quenching; purifying a mixture obtained by post-treatment, enabling the mixture to enter a water phase through salifying treatment in purification, extracting by using a small-polarity solvent to remove small-polarity impurities, weakening acidity to dissociate a crude product, and crystallizing again. According to the method disclosed by the invention, by virtue of acid-base salifying treatment of uracil, extraction and impurity removal of a small-polarity solvent and crystallization and purification processes, the production cost and the operation complexity are remarkably reduced while the yield of more than or equal to 80.6% and the purity of more than or equal to 99.10% are ensured, and large-scale industrial production of nucleoside compounds is facilitated.

The invention discloses a preparation method of litamilast, which comprises the following steps: a) carrying out primary carbonyl insertion reaction on a compound shown in a formula (II) and a compound shown in a formula (III) to obtain a compound shown in a formula (IV); b) performing trifluoromethanesulfonylation on the compound in the formula (IV) to obtain a compound in a formula (V); c) carrying out secondary carbonyl insertion reaction on the compound shown in the formula V and amino acid shown in the formula VI to obtain a compound VII, and salifying the compound VII and dicyclohexylamine VIII to obtain a litamilast dicyclohexylamine salt IX; and d) dissolving and dissociating the litamilast dicyclohexylamine salt (IX), acidifying and crystallizing to obtain a litamilast crude product, and refining to obtain a litamilast (I) finished product. The method has the advantages of short steps, mild conditions, avoidance of frequent use of group protection and deprotection, avoidance of use of toxic reagents or toxic gases, great reduction of the occurrence of side reactions, reduction of the generation of impurities, simple post-treatment and higher purity.

The invention relates to a preparation method of bis (fluorosulfonyl) imine salt. The method comprises the following steps: adding anhydrous ammonium fluoride and cation source fluoride into an organic solvent, and then dropwise adding a sulfonyl chloride solution; and after dropwise adding, continuously stirring, and carrying out reflux reaction for 5-20 hours to obtain the bis (fluorosulfonyl) imine salt. According to the method, hydrogen fluoride and sulfonyl fluoride are not adopted, meanwhile, the adverse effect of water of water-containing metal hydroxide or metal carbonate in the bis (fluorosulfonyl) imide salification reaction process on product purification is avoided, and efficient, low-cost and large-scale preparation of the bis (fluorosulfonyl) imide salt is achieved.

The application belongs to the field of pharmaceutical preparations and discloses a soothing pharmaceutical preparation and a preparation method thereof. The preparation method comprises the following steps: firstly, preparing synthetic naphazoline hydrochloride by using compound 1 containing a cyano group, wherein a composite solvent composed of toluene and ethyl acetate is used for condensation reaction in the synthesis process, and dilute hydrochloric acid is used for salt formation; secondly, preparing synthetic pheniramine maleate by using compound 2 containing a halogen group and compound 3 containing a cyano group, wherein a weak base catalyst is used for condensation reaction in the synthesis process; finally, adding functional additives, naphazoline hydrochloride and pheniramine maleate into water, stirring and dissolving, and filling to obtain the soothing pharmaceutical preparation, wherein the pH of the soothing pharmaceutical preparation is 5.7-6.3. The soothing pharmaceutical preparation prepared by the above method can effectively avoid the adverse influence of impurities in naphazoline hydrochloride and pheniramine maleate on the soothing effect.