63results about "Optically-active compound separation" patented technology

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

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.

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 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 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 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

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.

This invention discloses a chiral amino acid resolving agent for the preparation of trans-chiral indeneamine. Specifically, it provides a chiral amino acid derivative as a resolving agent for the resolution of trans-2,6-dimethyl-1-indeneamine to prepare (1R,2S)-2,6-dimethyl-1-indeneamine. The resolution process is conducted under mild conditions, using a widely available and inexpensive general-purpose solvent. (1R,2S)-2,6-dimethyl-1-indeneamine was obtained with high yield and high optical purity. The beneficial effects of this invention are: obtaining (1R,2S)-2,6-dimethyl-1-indeneamine with an ee value greater than 97% and a resolution yield greater than 95%. Due to the poor hydrophilicity of the resolving agent, it can be recycled with high recovery rate, the process has high repeatability, and it is easy to achieve industrial production.

The application discloses a synthesis method of dextrophenethylsulfonic acid D-p-hydroxyphenylglycine complex salt, which utilizes the inactive enantiomer levorotatory phenethylsulfonic acid to prepare the dextrophenethylsulfonic acid D-p-hydroxyphenylglycine complex salt through racemization, recycles and utilizes the originally discarded inactive enantiomer levorotatory phenethylsulfonic acid in the mother liquor, greatly reduces the cost of the dextrophenethylsulfonic acid D-p-hydroxyphenylglycine complex salt, and greatly reduces COD in the mother liquor, thereby reducing environmental protection treatment pressure.

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

The application provides a resolution method of clemastine fumarate intermediate, comprising the following steps: 1) reacting racemic N-methyl-2-(2-chloroethyl)pyrrolidine with a chiral resolving agent in a first organic solvent to obtain a diastereomeric salt solution; 2) purifying the material after the reaction in step 1) by cooling and crystallization, and filtering to obtain R-N-methyl-2-(2-chloroethyl)pyrrolidine resolving agent salt; 3) dissolving the R-N-methyl-2-(2-chloroethyl)pyrrolidine resolving agent salt obtained in step 2) in a second organic solvent-water two-phase system, adjusting the pH value to 9-13, then separating the organic phase, and concentrating to obtain R-N-methyl-2-(2-chloroethyl)pyrrolidine; wherein the chiral resolving agent is at least one selected from L-di(3,5-dinitrobenzoyl) tartaric acid and L-di-p-chlorobenzoyl tartaric acid. By using a specific chiral resolving agent, the resolution efficiency of racemic N-methyl-2-(2-chloroethyl)pyrrolidine is significantly improved, and combined with cooling and crystallization and two-phase acid adjustment replacement, the operation is simple, and the cost is controllable.

The invention discloses a preparation method of an amide local anesthetic key intermediate, which comprises the step of carrying out hydrogenation reaction on N-(2, 6-dimethylphenyl) pyridine-2-formamide and hydrogen in a continuous flow fixed bed reactor to generate N-(2, 6-dimethylphenyl) piperidine-2-formamide. The method has the beneficial effects that the danger of a kettle type hydrogenation process is avoided, the process is stable, the operation is simple, the raw material conversion is complete, alkylation impurities are extremely few, excessive hydrogenation impurities are avoided, the atom economy is higher, and the method is greener and more efficient; the HPLC purity of N-(2, 6-dimethylphenyl) piperidine-2-formamide obtained through the hydrogenation process is larger than 99.5%, alkylation impurities are smaller than 0.2%, excessive hydrogenation impurities are smaller than 0.1%, next-step reaction can be directly carried out without purification, the preparation yield can be greatly improved, and the method is especially suitable for industrial production and has the cost competitive advantage.

This invention relates to the preparation of high-purity levetiracetam (S)-2-(2-oxo-1-pyrrolidine)butyramide. The preparation of the high-purity levetiracetam begins with 2-(2-oxopyrrolidine-1-yl)butyric acid as the starting material. Through esterification and ammonolysis, a racemic levetiracetam is obtained, which is then resolved by R-mandelic acid to yield high-purity levetiracetam with a chiral content of over 99.9%, a chiral isomer content of less than 0.05%, and no chloride detected. The chiral isomer (R)-2-(2-oxo-1-pyrrolidine)butyramide recovered after resolution can be racemed and further resolved by R-mandelic acid for the preparation of levetiracetam, achieving a total yield of over 90%. The recovered R-mandelic acid can be reused repeatedly, significantly reducing the consumption of resolving agent. This reaction has a short procedure, is easy to operate, and has a stable yield, which significantly reduces the cost of preparing levetiracetam. In addition, it has a very high chiral content, making it suitable for large-scale industrial production.

The present application provides topical compositions comprising genipin derivatives of formula (I), which are useful, for example, as coloring agents in semi-permanent tattoos. [Formula 1] JPEG2026505978000077.jpg2937

This invention discloses a chiral covalent organic framework composite membrane prepared by in-situ growth and its applications. This invention uses [NALC] as a reference. X -TAPB-DVA COF S As a functionalized material, a chiral covalent organic framework composite membrane was prepared by a secondary in-situ growth method using terephthalaldehyde (PAD) as the linker and 1,3,5-tris(4-aminophenyl)benzene (TAPB) as the nucleation site. This chiral covalent organic framework composite membrane can resolve enantiomers of mandelic acid, warfarin, naproxen, and ibuprofen, exhibiting a wide resolution range and stable resolution performance.

The invention provides a preparation method of fenerenone and an intermediate thereof. The invention discloses a preparation method of a fenerenone intermediate 5, which comprises the following steps: step 1, in an organic solvent, carrying out resolution reaction on a fenerenone intermediate 2 and D-diphenyl tartrate to obtain a resolution salt, and then carrying out acid-base reaction on the resolution salt and alkali to obtain a fenerenone intermediate 3; 2, in an organic solvent, in the presence of acid, carrying out nucleophilic substitution reaction on the fenerenone intermediate 3 and triethyl orthoformate to obtain a fenerenone intermediate 4; and step 3, in a solvent, carrying out a hydrolysis reaction on the fenerenone intermediate 4 to obtain the fenerenone intermediate 5. The preparation method provided by the invention has the advantages of short reaction steps, high reaction total yield, simple and safe operation, simple post-treatment steps, high purity of the prepared product, low production cost and suitability for industrial production.

This invention relates to the application of quaternary ammonium bases in the preparation of dextrorotatory nicotine, wherein the structure of the quaternary ammonium base is shown in formula (I): [NR1R2R3R4] + OH ‑ (I) R1, R2, R3, and R4 are independently selected from C 1‑3 Alkyl groups, C3-C6 cycloalkyl groups. This invention uses a novel quaternary ammonium base as a catalyst. First, racemic nicotine is prepared simply and efficiently from natural, optically active S-nicotine as the initial raw material. Then, preparative liquid chromatography is used to resolve the racemic nicotine, finally yielding high-purity dextrorotatory nicotine (R-nicotine).

The present invention relates to processes for the enantiomeric enrichment of lactic acid or salt thereof obtained from waste recycling.

The invention relates to the technical field of medicine synthesis, in particular to a preparation method of a clemastine fumarate SS isomer impurity. The structural formula of the impurity is as shown in Figure 1. According to the invention, the clomastine fumarate SS isomer impurity is prepared, and the efficient preparation and separation confirmation of the impurity are of great significance to the subsequent quality control of the clomastine fumarate raw material medicine and the preparation of the clomastine fumarate raw material medicine. The preparation method provided by the invention is simple and feasible, liquid phase preparation is not needed, and the high-purity clemastine fumarate SS isomer impurity can be obtained through a simple process. According to the invention, convenience is provided for impurity analysis and research of the clemastine fumarate raw material medicine and the preparation of the clemastine fumarate raw material medicine.

The invention belongs to the technical field of medicine synthesis, and particularly relates to an intermediate compound of alasset hydrochloride, a preparation method of the intermediate compound and a preparation method of the alasset hydrochloride. The preparation method of the alasset, provided by the invention, is safe, environment-friendly and suitable for industrial production.

In one aspect, the present disclosure provides a method of synthesis for methylone HCl, with 3,4-methylenedioxypropiophenone (MDP) as the starting material. In another aspect, the present disclosure provides stereoisomers of methylone. In another aspect, the present disclosure provides phenethylamines or cathinones covalently bound to a chemical moiety in a prodrug form. The presently described prodrug form allows slow / sustained / controlled delivery of the parent phenethylamines or cathinones into the blood system in a manner that would increase the duration of therapeutic efficacy.