86results about "Organic racemisation" patented technology

The application provides a preparation method of finerenone and intermediates thereof. The application discloses a preparation method of a finerenone intermediate 5, which comprises the following steps: step 1: in an organic solvent, a resolution reaction is carried out between a finerenone intermediate 2 and D-tartaric acid diphenyl ester to obtain a resolution salt, then an acid-base reaction is carried out between the resolution salt and a base to obtain the finerenone intermediate 3; step 2: in an organic solvent, a nucleophilic substitution reaction is carried out between the finerenone intermediate 3 and triethyl orthoformate in the presence of an acid to obtain a finerenone intermediate 4; step 3: in a solvent, a hydrolysis reaction is carried out between the finerenone intermediate 4 to obtain the finerenone intermediate 5. The preparation method has the advantages of short reaction steps, high total reaction yield, simple and safe operation, simple post-treatment steps, high product purity, low production cost and suitability for industrial production.

The invention provides a method for regulating and controlling dynamic kinetic resolution of spiral polycyclic aromatic hydrocarbon based on an inorganic chiral surface and application, and the method comprises the following steps: S1, rotating a substrate clockwise or anticlockwise, and depositing an inorganic material on the substrate by adopting a physical vapor deposition method to obtain an inorganic chiral nano material layer; wherein the contact angle between the inorganic material and N, N-dimethylformamide is less than 22 degrees, and the deposition angle and the normal direction of the substrate form an angle of 86 degrees or 0 degree; s2, dissolving spiral polycyclic aromatic hydrocarbon molecules needing to be split into N, N-dimethylformamide to obtain a solution; then dropwise adding to the surface of the inorganic chiral nano material layer to obtain a sample; and S3, annealing the sample at 40-50 DEG C, and obtaining the homochiral aggregate after the solvent is completely evaporated. The technical scheme provided by the invention is high in controllability, strong in universality and good in stability, and can be used for efficiently preparing chiral compounds with specific configurations.

To provide a simple method for optically resolving a chiral compound, which is expected to be industrially applicable.SOLUTION: A method for optical resolution of a chiral compound includes dissolving a mixture of both enantiomers of the chiral compound in a first solvent to prepare a first solution, stirring the prepared first solution, precipitating a first gel in the stirred first solution, and separating the first solution into the first gel and a first supernatant.SELECTED DRAWING: Figure 1

The invention discloses an enantiomer crystallization resolution method of delta-dodecalactone, which comprises the following steps: hydrolyzing delta-dodecalactone under an alkaline condition for ring opening, acidifying to obtain 5-hydroxylauric acid, adding a dehydroabietylamine solution, dissolving in an alcohol solvent or a solvent system consisting of the alcohol solvent and other solvents, fully reacting, cooling, slowly crystallizing, filtering, washing, and drying to obtain the delta-dodecalactone enantiomer. Filtering, adding ethyl acetate and hydrochloric acid into a filter cake for dissolving, carrying out liquid-liquid extraction and washing an organic phase, and carrying out rotary evaporation concentration on the organic phase to obtain optically enriched delta-dodecalactone; the method is simple to operate and does not depend on expensive special equipment, and the sample loading amount is greatly increased; due to the introduction of dehydroabietylamine, the 5-hydroxylauric acid and the dehydroabietylamine form diastereoisomer salt, and chiral separation is carried out in the crystallization process; the reaction safety is high, and the requirements of green chemistry are met.

This invention provides a method for preparing chiral epoxy compounds, chiral β-lactones, and polyhydroxyalkanoates. The method involves three steps: chiral resolution of the epoxy compound, carbonylation of the chiral epoxy compound to prepare a chiral β-lactone, and ring-opening polymerization of the β-lactone. Using this method, polyhydroxyalkanoates with good tensile strength and toughness, as well as a wide processing window, can be prepared. This invention has advantages such as simple steps, low raw material costs, and no need to introduce a second monomer, making it easy to scale up production.

This invention belongs to the field of recycling and purification technology, specifically relating to a method for recovering the β isomer from a CME solution containing both β and α isomers. The method includes the following steps: concentrating the CME solution containing both β and α isomers and dissolving it in methanol with trichloroacetic acid to form a salt, followed by cooling and crystallization and filtration to obtain the trichloroacetic acid salt of the CME β isomer; then, ionizing the trichloroacetic acid salt of the CME β isomer in methanol with ammonia to obtain the CME β isomer. By reacting trichloroacetic acid with the α and β isomers of CME to form a salt, the different solubilities of the trichloroacetic acid salts of the α and β isomers are utilized to separate the trichloroacetic acid salt of the CME β isomer, and then ionizing the trichloroacetic acid salt of the CME β isomer with ammonia, the CME β isomer is recovered.

The present invention relates to a preparation method for tert-butyl (R)-3-amino-1-oxa-8-azaspiro[4.5]decane-8-carboxylate, comprising the following steps: enabling N-BOC-4-piperidone to undergo a Grignard reaction with allylmagnesium halide to obtain intermediate 1; enabling the intermediate 1 to undergo a substitution reaction with 3-halopropene to obtain intermediate 2; enabling the intermediate 2 to undergo an olefin metathesis reaction under the action of a Grubbs catalyst to obtain intermediate 3; enabling the intermediate 3 to undergo a nitration reaction with nitric acid to obtain intermediate 4; enabling the intermediate 4 to undergo a hydrogenation reduction reaction to obtain racemic intermediate 5; and enabling the intermediate 5 to undergo chiral resolution by means of a resolving agent to obtain a target product. The preparation method provided by the present invention has a short process route, simple operation, and no substantial waste water and waste gas generated, and can achieve relatively high total product yield and chemical and chiral purities.

The present invention relates to an improved, efficient, scalable process to prepare intermediate compounds, such as compound 5M, having the structure useful for the synthesis of compounds that target KRAS G12C mutations, such as

The invention relates to the field of organic synthesis, in particular to a synthetic method of (2R, 4S)-N-BOC-4-hydroxypiperidine-2-methyl formate. The synthesis method of (2R, 4S)-N-BOC-4-hydroxypiperidine-2-methyl formate comprises the following steps: mixing a material A, a material B, potassium carbonate, sodium iodide and a solvent, and reacting to obtain a material C; mixing the material C, the material D, triethylamine and a solvent, and reacting to obtain a material E; mixing the material E, ammonia water and a solvent, and reacting to obtain a material F; and mixing the material F, di-tert-butyl dicarbonate, a palladium carbon catalyst and a solvent, and carrying out a reaction to obtain the (2R, 4S)-N-BOC-4-hydroxypiperidine-2-methyl formate. The process route is easy to operate and has no special dangerous reaction. Reaction materials are cheap and easy to obtain, and the prepared product is high in purity.

Provided is an amine separation method that includes separating an amine through chromatography using a stationary phase including a ligand having a crown ether-like cyclic structure and being supported on a carrier; and a mobile phase containing a salt of a cation and an acid anion at a concentration of 0.2 mM or more and 50.0 mM or less and containing a solvent having a water content of 50 vol. % or less.

The application discloses a preparation method of a non-nelirige intermediate 3, which comprises the following steps: carrying out a resolution reaction on non-nelirige intermediate 2 and D-tartaric acid diphenyl ester in an organic solvent to obtain a resolution salt, and then carrying out an acid-base reaction on the resolution salt and a base to obtain the non-nelirige intermediate 3. The preparation method has the advantages of short reaction steps, high total reaction yield, simple and safe operation, simple post-treatment steps, high product purity, low production cost and suitability for industrial production.

The invention provides atomoxetine hydrochloride and a preparation method thereof, and relates to the technical field of medicinal chemistry and organic synthesis. The method provided by the invention comprises the following steps: adopting acetophenone, methylamine hydrochloride and a formaldehyde aqueous solution as raw materials, carrying out Mannich reaction to construct a beta-amino carbonyl skeleton, reducing carbonyl into hydroxyl by adopting sodium borohydride, then reacting with di-tert-butyl dicarbonate to form an amino protecting group, adopting o-methylphenol as a raw material, and preparing the beta-amino carbonyl skeleton. The method comprises the following steps: adding p-toluenesulfonic acid monohydrate and a (2-hydroxybenzyl) phosphine oxide catalyst to construct an ether bond through a Mitsunobu reaction, then removing a t-butyloxycarboryl protecting group, and carrying out chiral resolution and salinization reaction by using S-mandelic acid to obtain atomoxetine hydrochloride. The method of dropwise adding the formaldehyde aqueous solution in batches and controlling the reaction temperature is adopted, so that the generation of impurities can be reduced, and the yield is effectively improved; the p-toluenesulfonic acid monohydrate and the (2-hydroxybenzyl) phosphine oxide catalyst capable of participating in catalytic circulation are used for catalyzing the Mitsunobu reaction, the economic principle is met, and the purity and the yield of the product are greatly improved.

This invention discloses a method for preparing atomoxetine hydrochloride. Specifically, it includes: (1) using compound I and compound II as raw materials, etherifying them to obtain compound III; (2) reacting compound III and a chiral resolving reagent solution in a microchannel reactor 1 to obtain compound IV; (3) reacting the filtrate from the previous step in a packed bed reactor to obtain a solution of compound III, which can be used to prepare compound IV in step (2); (4) converting compound IV prepared in step (2) into hydrochloride to obtain atomoxetine hydrochloride (compound V). The dextrorotatory isomer (compound VI) is repeatedly racemized and resolved using this method, increasing the theoretical yield from 50% to over 90%. Moreover, the racemate continuously generated in step (3) and the racemate obtained in step (1) can be processed simultaneously using a microchannel continuous reactor, avoiding the cumbersome process of multiple separate resolving processes, reducing equipment wear and shortening the production cycle.

The application discloses a method for separating spirodiphenol by using an analog moving bed chromatography. The method for separating spirodiphenol specifically disclosed comprises the following steps: separating left-handed spirodiphenol and right-handed spirodiphenol from a spirodiphenol racemate by using an analog moving bed chromatography system; and the analog moving bed chromatography system has the following conditions: a stationary phase: silica gel coated with chiral polymer; and a mobile phase: a mixed solution of n-hexane and ethanol. The application can realize complete separation of two single enantiomers, obtain high purity and high recovery rate, and is more suitable for industrial production while being continuously operated. The process has strong stability, constant product quality, high automation degree, higher yield and lower cost than batch chromatography. The method also has the advantages of high yield, low cost, recyclable elution phase, green environmental protection, automatic and continuous production, stable product quality and the like.

The present invention discloses a method for resolving cyclohexylphenyl glycolic acid and the preparation of optically active phenylcyclohexyl glycolate esters. More particularly, the invention provides a process for preparation of optically active R-oxybutynin hydrochloride with high enantiomeric purity of greater than 99%.

The invention discloses a DL-phenylethylamine resolution process, which belongs to the technical field of chemical engineering, and comprises the following steps: S1, resolution: heating D-glutamic acid and DL-phenylethylamine in a mixed solvent of methanol and water to react, then cooling to crystallize, filtering and drying to obtain a composite salt, S2, D-glutamic acid recovery: dissolving the composite salt obtained in the step 1 in water, and recovering the DL-glutamic acid to obtain the DL-phenylethylamine. And S3, dissociation: regulating the pH value of the mother liquor after the D-glutamic acid is recovered in the step 2 to 12 by using alkali, standing for layering, taking an upper oil layer, and distilling to obtain the S (-)-alpha-phenylethylamine. According to the present invention, the S-(-)-alpha-phenylethylamine is successfully efficiently prepared by using the D-glutamic acid as the resolving agent, the product yield is 81.8%, the optical rotation is-38.2 degrees, the optical purity is excellent, the resolving agent recovery rate is as high as 88.1%, the expensive catalyst or the complex equipment is not required, and the industrial implementation is easy.

The application discloses a preparation method of (2R, 5S)-4-Boc-2, 5-dimethyl piperazine. Trans-2, 5-dimethyl piperazine is used as raw material, reacts with di-tert-butyl dicarbonate to generate N-Boc-2, 5-dimethyl piperazine, then is subjected to splitting by L-(+)-mandelic acid to obtain (2R, 5S)-4-Boc-2, 5-dimethyl piperazine mandelic acid salt, and then is separated to obtain 2R, 5S)-4-Boc-2, 5-dimethyl piperazine. The raw material used in the application is cheap and easy to obtain, the reaction condition is mild, the operation is simple, the total reaction yield is high, and the application is suitable for industrial production.

The invention discloses an enantioselective reverse micelle extraction and resolution method of a phenylethanolamine raceme drug. According to the method, an enantioselective reversed micelle formed by a carbamyl amino acid chiral surfactant in a non-aqueous solvent is used as a chiral recognition agent, the enantioselective reversed micelle and one enantiomer of a phenylethanolamine raceme drug aqueous solution are preferentially subjected to specific recognition and selectively extracted to an organic phase, and the other enantiomer is left in the aqueous phase; therefore, chiral resolution is realized. The resolution method of the phenylethanolamine racemate drug has the characteristics that the resolution process is simple, the chiral surfactant can be recycled and reused, the cost is low, the method is green and environment-friendly, and the requirement of large-scale resolution is met.

The invention discloses a chiral chemical resolution method for an L-5-methyltetrahydrofolic acid intermediate, which comprises the following steps: selecting a 9-10-dehydrofolic acid furanamine hydrochloride racemate as a raw material, forming a diastereomer by using the racemate, and separating the diastereomer from the 9-10-dehydrofolic acid furanamine hydrochloride racemate to obtain the L-5-methyltetrahydrofolic acid intermediate. And refining, separating and purifying to obtain the monomer tetrahydrofolate with high chiral purity. And carrying out reductive amination on the monomer salt to form a calcium salt, thereby obtaining the target product L-5-methyl calcium tetrahydrofolate. According to the chiral chemical resolution method for the L-5-methyltetrahydrofolate intermediate, the synthesis process is simplified, the synthesis process of the calcium L-5-methyltetrahydrofolate is easy to control, the situation that the final yield is low due to deterioration of materials in the resolution process is not prone to occurring, the cost is low, coenzyme and a regeneration system thereof do not need to be used, and the method is suitable for industrial production. According to the method, the reaction process is easy to implement, a special catalyst is not needed, the cost is reduced, meanwhile, the method is suitable for large-scale industrial production, and a foundation can be provided for application of the L-5-methyltetrahydrofolate calcium.

The application belongs to the technical field of medicine and chemical industry, and particularly discloses a synthesis method of chiral epichlorohydrin.The chiral Salen Co(II) is in-situ oxidized, and then is reacted with TsOH or PhSO3H to obtain a catalyst Salen Co(III) OTs or Salen Co(III) SO3Ph, which is used to catalyze the asymmetric kinetic resolution of racemic epichlorohydrin and TsOH or PhSO3H at a certain temperature, and chiral epichlorohydrin is obtained at a high yield.In addition, the reaction raw material and the catalyst can be recycled and reused.

Processes for preparing (1S,3R)-3-(4-((R)-2-chloro-8-methyl-8-(trifluoromethyl)-7,8- dihydro-6H-pyrazolo[1,5-a]pyrrolo[2,3-e]pyrimidin-6-yl)phenyl)-2,2-difluoro-1-methyl-N- ((trans)-3-(methylsulfonyl)cyclobutyl)cyclopropane-1-carboxamide are described, which are useful for commercial manufacturing. The compound may be useful for the treatment of a disease, syndrome, condition, or disorder, particularly a MALT1- related disease, syndrome, condition, or disorder, including but not limited to, cancer and immunological diseases.

The invention discloses a method for separating EHB enantiomers based on a collaborative chiral recognition chromatography system, and belongs to the technical field of chiral compound separation. Comprising the following steps: dissolving L-proline and copper salt in a mixed solution of an organic solvent and water, and adding alkali to adjust the pH value to 7.0-7.8 to prepare an L-proline-copper (II) chiral complexing mobile phase; enabling the sample to flow through a chromatographic column filled with a polysaccharide derivative chiral stationary phase, and establishing a synergetic chiral recognition environment; the method comprises the following steps: adding L-proline into an organic solvent, introducing a (R, S)-EHB sample, carrying out elution separation, respectively collecting (R)-EHB and (S)-EHB fractions, removing copper ions through cation exchange resin, and recovering L-proline. The chiral synergistic effect of the stationary phase and the mobile phase is utilized, the enantiomer separation effect is remarkably enhanced, the optical purity ee value is larger than or equal to 99.0%, the recovery rate is larger than or equal to 95%, L-proline can be recycled, and the method has the advantages of being efficient, environmentally friendly and low in cost.

To provide improved synthesis of a key intermediate of a KRAS G12C inhibitor compound.SOLUTION: The present invention relates to an improved, efficient, scalable process to prepare intermediate compounds, such as compound 5M, having the structure of the lower formula in the figure, useful for synthesis of compounds that target KRAS G12C mutations, such as the upper formula in the figure.SELECTED DRAWING: Figure 1

The invention relates to the technical field of fine chemical engineering, in particular to a method for green production of D-tartaric acid by a double-compartment bipolar membrane process, which comprises the following steps: preparing a raw material sodium tartrate solution generated by hydrolysis of a sodium epoxysuccinate solution through a strain into a raw material solution with the mass concentration of 7-8.5%, and carrying out electrodialysis on the raw material solution through a double-compartment bipolar membrane electrodialysis device to obtain D-tartaric acid. Directional ion migration is realized under the action of direct current; sodium ions enter an alkali side through a positive membrane and are combined with hydroxyl ions generated by dissociation of a bipolar membrane to generate a sodium hydroxide solution with the mass concentration of 3-4%; hydrogen ions enter an acid side through the bipolar membrane and are combined with tartrate ions to generate a D-tartaric acid solution, and a D-tartaric acid finished product is obtained through subsequent concentration and drying; through the mode, one-step conversion from sodium tartrate to D-tartaric acid is realized, the cost is reduced, and the yield is improved.

The application discloses a modified corn protein zein chiral separation membrane and belongs to the technical field of functional high polymer materials. The modified corn protein zein chiral separation membrane is prepared by the following steps: 1) mixing and stirring nano corn protein zein, chiral resolution material and an ethanol solution, adding acid to adjust the pH to 5-10, and then performing ultrasonic oscillation, and then flowing the solution on a film preparation plate to form a nano membrane material; the chiral resolution material is polysaccharide or a supramolecular compound; 2) drying and peeling the nano membrane material to obtain the modified corn protein zein chiral separation membrane. The modified corn protein zein chiral separation membrane provided by the application has high separation performance when applied to the separation of racemic compounds.

This invention discloses a method for synthesizing ferrocene-isoquinoline and ferrocene-dihydroisoquinoline planar chiral compounds, belonging to the field of asymmetric catalysis technology. Using chiral phosphoric acid (CPA) as a catalyst, 1,4-dihydropyridine compound (HEH) as a hydrogen source, and racemic ferrocene-isoquinoline derivative (+ / -)-1 and ditert-butyl dicarbonate as substrates, two types of planar chiral ferrocene compounds are synthesized through asymmetric transfer hydrogenation resolution. The enantiomeric excess of the ferrocene-isoquinoline planar chiral compounds can reach 95%, while the enantiomeric excess of the ferrocene-dihydroisoquinoline carboxylic acid tert-butyl ester planar chiral compounds can reach 89%, with a resolution coefficient (S value) reaching 50. This invention achieves the hydrogenation kinetic resolution of ferrocene-isoquinoline compounds, is simple to operate, uses commercially available catalysts, operates under mild reaction conditions, and exhibits good resolution effects, showing excellent application prospects.

The invention provides a method for resolving diastereoisomers of amino phosphaphenanthrene compounds, and belongs to the technical field of organic chemistry. The resolution method provided by the invention is realized by utilizing the dissolvability difference of the two groups of diastereoisomers, and the resolution of the two groups of diastereoisomers of the compound can be realized by adding a proper amount of the amino phosphaphenanthrene compound into a common solvent through simple stirring and filtering operations. Compared with the traditional method, the method provided by the invention avoids tedious experimental operation steps and use of expensive splitting instruments. And the splitting steps are simple. According to the diastereoisomer of the obtained amino phosphaphenanthrene compound, the absolute configuration of a molecule is determined through single crystals, and the diastereoisomer has a photoluminescence characteristic and an aggregation-induced emission effect and shows a wide application prospect in the field of photoelectric functional materials.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a resolution method of an azacyclo derivative, which comprises the following steps: carrying out salt forming reaction on 5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1, 2, 4-triazole-5-yl)-2, 7, 8, 9-tetrahydro-3H-pyrido [4, 3, 2-de] phthalazin-3-one racemate and chiral acid, and carrying out crystallization resolution to obtain (8S, 8S)-1, 2, 4-triazole-5-yl)-2, 7, 8, 9-tetrahydro-3H-pyrido [4, 3, 2-de] phthalazin-3-one. According to the present invention, the (1R, 9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1, 2, 4-triazole-5-yl)-2, 7, 8, 9-tetrahydro-3H-pyridino [4, 3, 2-de] phthalazin-3-one is synthesized by using the method, the resolution method is simple, the production cost can be effectively reduced, the production efficiency can be improved, and the method is suitable for industrial production.

The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for chiral resolution of a clodinafop-propargyl enantiomer. According to the present invention, the high performance liquid chromatography-mass spectrometry technology is adopted to separate the clodinafop-propargyl enantiomer, the chromatographic column is the polysaccharide derivative chiral chromatographic column, the mobile phase A is the organic solvent, the mobile phase B is pure water, the volume ratio of the mobile phase A to the mobile phase B is 40: 60-100: 0, isocratic elution is performed, the column temperature is 30-35 DEG C, and the flow rate is 0.5-0.8 mL / min. The invention provides the method for effectively separating the chiral propargyl enantiomer, and the method has the advantages of high sensitivity, simplicity in operation, high separation speed and the like.

The invention discloses a preparation method of (R)-3-piperidinecarboxamide with high optical purity, which comprises the following steps: adding racemic 3-piperidinecarboxamide and a resolving agent into an organic solvent, heating to 50-80 DEG C for reaction, and after the reaction is finished, filtering while hot to obtain a resolving agent salt of (R)-3-piperidinecarboxamide; the resolving agent is tartaric acid and derivatives thereof. The (R)-3-piperidinecarboxamide and the salt thereof with high optical purity can be obtained, the raw materials are low in price, and the production cost is greatly reduced.