154results about "Preparation by rearrangement reactions" patented technology

The invention relates to the medicine chemical synthesis field, and especially discloses a preparation method of a Ticagrelor intermediate. The preparation method comprises the following steps: 1) taking 3,4-difluorobenzaldehyde (I) as an initial raw material, reacting with a phosphorus ylide material liquid to obtain (E)-3-(3,4-difluorophenyl)-2-acrylic acid ester (II); 2) performing a Simons-Smith asymmetric cyproteronethe reaction on the (E)-3-(3,4-difluorophenyl)-2-acrylic acid ester (II) to obtain trans-(1R,2R)-2-(3,4-difluorophenyl) cyclopropanecarboxylic acid ester (III); 3) performing aminolysis on the trans-(1R,2R)-2-(3,4-difluorophenyl) cyclopropanecarboxylic acid ester to obtain trans-(1R,2R)-2-(3,4-difluorophenyl)cyclopropanecarboxamide (IV); and 4) performing a Huffman rearrangement reaction on the trans-(1R,2R)-2-(3,4-difluorophenyl)cyclopropanecarboxamide (IV) to obatain the Ticagrelor intermediate (V). The method of the invention has the advantages of simple process, convenient operation, mild reaction condition and easy control, low cost and easy acquisition of raw material, high product yield and product purity, and is adapted to large scale industrial production.

The invention discloses a method for preparing a ticagrelor key intermediate VII and a racemate thereof. The method comprises the following steps: by using a compound V or a racemate thereof as a raw material, performing acidic hydrolysis to obtain a compound VI or a racemate thereof; and performing Curtis rearrangement to obtain a compound VII or a racemate thereof. According to the ticagrelor key intermediate and the racemate thereof prepared by the method, the adopted initial raw materials are low in price and readily available, the requirements of reaction conditions on solvents are low, the operation is safe, simple and convenient, and the method is environment-friendly; moreover, when the ticagrelor key intermediate and the racemate thereof are prepared by adopting a special intermediate, the after-treatment is simple and convenient, and the large-scale production is more easily realized.

The invention is a manufacturing method of diamante amine hydrochlorate. The invention adopts 1, 3-dimethyl adamantine to reacts with tert-butylchlorine and gets 1-chlorine-3, 5-dimethyl adamantine; then reacts with acetamide directly, the educt from water reacts with sodium hydroxide in ethanediol or glycerine solvent, extracts by acetic ester, condenses, and blow in dry hydrochloride gas and gets the coarse product. There gets the pure product through alcohol-acetic ester recrystallization.

The invention relates to a method for preparing trans-aryl cyclopropanecarbonitrile with a structure shown in a formula (IV) in the specification through reaction between aryl substituted ethylene oxide and cyan substituted phosphate and further relates to a method for preparing cyclopropylamine from trans-aryl cyclopropanecarbonitrile. Trans-aryl cyclopropanecarbonitrile and cyclopropylamine are used for preparing drugs, especially ticagrelor.

The invention relates to a preparation method of 2,2'-bis(trifluoromethyl)-4,4'-diaminodiphenyl. The preparation method comprises the following steps: synthesizing 3,3'-bis(trifluoromethyl)hydrazo-benzene in an inorganic alkaline aqueous solution by adopting nitrobenzotrifluoride as a raw material, adopting a phase transfer catalyst, a co-catalyst and Pd/C as a catalytic system and adopting aromatic hydrocarbon as a solvent, and performing the re-arrangement reaction on the 3,3'-bis(trifluoromethyl)hydrazo-benzene in an inorganic acid aqueous solution, thus obtaining 2,2'-bis(trifluoromethyl)-4,4'-diaminodiphenyl, wherein the phase transfer catalyst is one or a mixture of more of sodium dodecyl benzene sulfonate, sodium dodecyl sulfate and cetyl trimethyl ammonium bromide, and the co-catalyst is one or a mixture of more of 2,3-dichloro-1,4-naphthoquinone, 2-hydroxyanthraquinone and 2,6-dioxyanthraquinone. The preparation method has the advantages of mild reaction condition, simple process, high product quality and yield, low production cost, environmental friendliness, suitability for continuous production and the like.

The invention relates to a method and a device for preparing diphenylmethane series diamine and polyamine with low N-methyl impurity content and a catalyst. The method comprises the steps as follows:a) phenylamine and formaldehyde are subjected to a condensation reaction in the presence of an acid catalyst, and a reaction mixture containing polyamino benzylaniline salt is obtained; b) the reaction mixture from a) enters a fixed bed reactor loaded with the catalyst for a transposition rearrangement reaction, a mixture containing diphenylmethane series diamine salt and polyamine salt is obtained after the reaction, and active components of the transposition rearrangement reaction catalyst comprise one or more of vanadium phosphate oxide, a Nb2O5-La2O3 solid solution and a Pr2O3-Ce2O3 solidsolution. The reaction selectivity at the transposition rearrangement stage can be improved, so that the content of N-methyl MDA impurities in the product can be decreased, the product quality can besubstantially improved, and the N-methyl MDA content can be decreased to 0.01% or below.

The invention discloses a synthetic method for an intermediate compound (I) of ticagrelor and a mandelate compound(VI) thereof. Asymmetric reduction is carried out by the enzymic method; the synthetic method has the advantages of simple operation, mild reaction condition, little pollution, high yield of the product, good optical purity, thus the synthetic method is suitable for large-scale production; the energy consumption and the discharge of organic waste-water are greatly reduced, and requirements of large-scale industrial production are met well.

A method for preparing (1R, 2R)-2-(3, 4-difluoro phenyl)cyclopropylamine includes the steps of: taking 1,2-difluorbenzene as a raw material, and introducing chloracetyl on a benzene ring through the Friedel-Crafts reaction; carrying out reduction by using a boron hydrogen compound, then carrying out a dead circulation reaction, and obtaining a racemate 3,4-difluoro phenyl epoxyethane; carrying out hydrolysis reaction on the racemate 3,4-difluoro phenyl epoxyethane and water in the action of a catalyst to form (s)-3,4-difluoro phenyl epoxyethane; and carrying out reaction on the (s)-3,4-difluoro phenyl epoxyethane and phosphoryl triethyl acetate, then carrying out ammonolysis and Hofmann degradation reactions, and obtaining the (1R, 2R)-2-(3, 4-difluoro phenyl)cyclopropylamine. The method can avoid using expensive reagents during chirality redox, and obtains the (s)-3,4-difluoro phenyl epoxyethane through the kinetic resolution. The raw material cost is low, and the catalyst can be recycled. The (s)-3,4-difluoro phenyl epoxyethane can be obtained by configuration conversion of resolution generated R-configuration, and intermediate cost can be reduced.

A novel stereochemical mixture of 1,6-diaryl-2,5-diaminohexanes, such as a mixture of stereoisomers of 1,6-diphenylhexane-2,5-diamine, is described. Also described are methods of preparing stereochemically pure 1,6-diaryl-2,5-diaminohexanes, and particularly stereochemically pure 1,6-diphenyl-2,5-diaminohexane. Also described is the use of both the mixture of stereoisomers and the individual stereoisomers.

An organic compound with characteristics excelling in hole-injecting/transporting performance and having an electron blocking ability, a highly stable thin-film state, and excellent heat resistance is provided as material for an organic electroluminescent device of high efficiency and high durability, and the organic electroluminescent device of high efficiency and high durability is provided using this compound. The compound of a general formula (Chemical Formula 1) having a substituted acridan ring structure is used as a constituent material of at least one organic layer in the organic electroluminescent device that includes a pair of electrodes and one or more organic layers sandwiched between the pair of electrodes.

The invention discloses a method for preparing (1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine. The method comprises the following steps: carrying out a Fuke acyl reaction on 3,4-difluorobromobenzene (compound 2) which serves as a raw material and chloroacetyl chloride under conditions of lewis acid and certain temperature to obtain a compound 3; carrying out stereoselective reduction to obtain a compound 4; carrying out cyclization, olefination, hydrolyzation and debromination to obtain a compound 8; and preparing amide, and carrying out Hoffmann elimination to obtain a target compound 1. According to the method, the traditional preparation process is improved, the (1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine can be effectively, simply and conveniently prepared, the total yield is relatively high, the stereoselection is relatively high, and the intermediate in each step is easily purified and stored. The reaction formula in the method is as shown in the specification.

The inventiondiscloses a preparation method of ticagrelor. The method comprises the following steps: (1) reducing a compound shown in a formula III in the presence of a proton source provided by sodium borohydride or potassium borohydride and diethyl aniline hydrochloride to obtain a compound shown in a formula IV; (2) reacting the compound IV in the presence of alkali to generate a compound VI; (3) hydrolyzing the compound VI without purification to generate a compound VII; (4) reacting the compound VII to generate acyl chloride, reacting the acyl chloride to generate formamide, thus obtaining a compound shown in a formula IX; and (5) carrying out Hofmann rearrangement on the compound IX to obtain a compound shown in a formula II. Regents used in the method are nontoxic, harmless, environmentally friendly and low in price; the used key reagents can be recycled. Therefore, the method is applicable to industrial production.

The invention relates to the field of organic synthesis and especially relates to a preparation method for pentafluorophenol. The preparation method comprises the steps of: 1) a Hoffmann rearrangement reaction: performing the rearrangement reaction to the compound (II) in the presence of alkali and a halogenation reagent to prepare the compound (III); 2) a diazo-hydrolysis reaction: performing a diazotization reaction to the compound (III) with a nitroso compound and performing a hydrolysis reaction in the presence of a catalyst to prepare the compound (I). The raw materials in the method are easy to obtain. The preparation method is short in synthesis route and is mild in reaction conditions, is simple in purification of the product, has high product purity and stable product quality, is low in cost of the whole synthesis route and is suitable for industrial large-scale promotion and application.

The invention relates to a synthetic method for 4,4'-dihalogenated-3,3'-dialkyl(alkoxyl) biphenyl compounds. The method employs o-nitro alkyl (alkoxyl) benzene as an initial raw material, 2,2'-dialkyl(alkoxyl) hydrazobenzene is prepared through catalysis hydrogenation in an alkaline environment, hydrochloric acid acidifying rearrangement is carried out, 4,4'-diamino-3,3'-dialkyl(alkoxyl) biphenyl is prepared, finally, a diazotization reaction is carried out and 4,4'-dihalogenated-3,3'-dialkyl(alkoxyl) biphenyl compounds are prepared. The synthetic method is advantaged by cheap and easily available raw materials, mild reaction conditions, simple operation, high safety coefficient, high yield and low cost.

The invention provides a preparation method of pentafluoroaniline. The preparation method is characterized by comprising the following steps of: (1) adding pentafluorobenzonitrile into sulfuric acid with the concentration of 70-98% for hydrolysis, controlling the hydrolysis temperature to be 70-120 DEG C and the reaction time to be 3-5 hours, and then adding the product into water to separate out, and filtering to obtain pentafluorobenzamide; and (2) mixing the pentafluorobenzamide prepared by step (1) with alkali solution and halogen or hypohalite, preserving the heat for 4-6 hours at -10 to 20 DEG C and then heating up to 70-110 DEG C to carry out Hoffman degradation, controlling the reaction time to be 0.5-3 hours, and then performing steam distillation to obtain the pentafluoroaniline. The method provided by the invention has the advantages that the raw materials are easily available, the process is simple, the operation is convenient, the product purity is high (99% or higher), the yield is high (as high as over 80%), the cost is low, and the method is safe and efficient with energy conservation, consumption reduction and little discharge of three wastes, so the method provided by the invention is suitable for industrial production on a large scale.

Disclosed is a process for the preparation of amines by continuously feeding a carboxamide, aqueous alkaline hypohalite, and aqueous alkaline hydroxide to a first reaction zone to form a N-halocarboxamide, measuring the concentration of at least one reaction component in the effluent from the first reaction zone, and using the result of that measurement to control the feed rate of at least one of the feed components of to achieve at least 90% conversion of the carboxamide in the first reaction zone. The effluent from the first reaction zone is fed continuously to a second reaction zone where it further reacts to form an aqueous solution of an amine. The effluent from the second reaction zone may be fed continuously to a distillation column. The process is particularly useful for the preparation of cyclopropylamine.

A process for preparing high molecular weight acyclic polyamines comprising providing a reaction mixture that includes at least a first component comprising a first organic, nitrogen-containing compound that contains at least two non-tertiary amine groups separated from one another by a ternary or higher carbon atom spacing that can be transaminated in the presence of a hydrogenation/dehydrogenation catalyst to form a mixture of higher molecular weight, acyclic polyamines while minimizing the formation of cyclic polyamines.

The invention provides a method for preparing phenylaniline, which comprises the following steps: mixing cyanophenyl shown in the formula II, first alkaline compounds, nickel catalysts and borophenylic acid shown in the formula III or borophenylic esters shown in the formula VI to carry out suzuki coupling reaction for obtaining cyanobiphenyl shown in the formula IV; mixing the cyanobiphenyl, second alkaline compounds and oxyful, and hydrolyzing the cyanobiphenyl to obtain amido biphenyl shown in the formula V; and mixing the amido biphenyl, third alkaline compounds and sodium hypohalite to generate Hofmann degradation reaction for obtaining phenylaniline shown in the formula I, wherein R1 is chlorine, bromine, iodine, sulphonic acid ester radicals, carbonic ether radicals or alkyl ester radicals; R2 is alkyl, alkoxy, cyano, amido or hydrogen; R3 is chlorine, bromine or iodine; and R4 is alkyl, alkoxy, cyano, amido or hydrogen. The preparing method provided by the invention has the advantages of mild condition, low cost, cleanness and environment protection.

The invention discloses a preparation method of p-phenylenediamine, which comprises the following steps of: 1) ammonolysis: crushing waste polyester drink bottles, and mixing the crushed polyester drink bottle with ethylene glycol and liquid ammonia and stirring for reaction to obtain terephthalamide; 2) chlorination: reacting terephthalamide to react with chlorine to obtain a chloride; and 3) hofmann degradation: heating the water solution of chloride product NaOH or KOH, and carrying out the hofmann degradation to obtain p-phenylenediamine. In the ammonolysis and chlorination, mother liquor is applied, so that the yield is increased, and the consumption of raw material is reduced. In the degradation process, brown waste water contains more p-phenylenediamine. The p-phenylenediamine is extracted from the waste water by a solvent, so that the yield is increased, and the pollution control cost is reduced. The p-phenylenediamine is prepared in a way of waste ester regeneration, so that the problem of waste treatment in a environment-friendly manner is solved; furthermore, the content of isomer in the polyester is very low, so that the produced p-phenylenediamine contains little isomer, and the product is high in quality.

An object of the present invention is to provide processes for producing an antiaging agent, a vulcanization accelerator and a modified natural rubber, which are environmentally friendly and capable of making provision against a decrease of petroleum resources in the future. An antiaging agent, a vulcanization accelerator or a modified natural rubber is produced by a method comprising: converting glucose into benzoic acid or a benzoic acid derivative by a microorganism or extracting benzoic acid or a benzoic acid derivative from a plant; and converting the obtained benzoic acid or benzoic acid derivative into aniline or an aniline derivative.

A process for preparing 3,3'-dichlorobiphenylamine hydrochloride includes such steps as mixing 2,2'-azobenzene dichlorohydride with arylhydrocarbon solvent, cooling, adding the solution to cooled solution of hydrochloric acid, translocation reaction, mixing the resultant with water or dilute solution of hydrochloric acid, washing, liquid-liquid separation to obtain lower-layer water phase 3,3'-dichlorobiphenylamine hydrochloride and upper-layer oil phase arylhydrocarbon solution, separating said water phase and refining.

The invention discloses a synthetic method of an N-substituted ethylene diamine derivative as structure fragments for various drugs. The method comprises the following steps: first performing Michael addition reaction on aromatic amine or fatty amine or heterocyclic amine and ethyl acrylate, then performing hydrazinolysis, and finally performing Curtius rearrangement reaction, thus preparing the target compound. The method has the advantages of low cost, moderate conditions, easy operation, high total yield and the like.

The invention provides a preparation method of an adamantane amine derivative. The preparation method comprises the following steps: performing an amidation reaction on an adamantane formic acid compound to generate an adamantane amide formate compound, and then reacting the adamantane amide formate compound with a heterocyclic aromatic halogenated substance, an aryl halogenated substance, an aliphatic alkyl halogenated substance, a halogen molecular, a metal or metalloid reagent or a high-valence iodide in the presence of additives under the catalytic action of a transitional metal catalyst, thereby generating an adamantane formamide C2 derivatization product; next, performing a hydrolysis reaction on the adamantane formamide C2 derivatization product to obtain an adamantane carboxylic acid derivative; and finally, performing a rearrangement reaction on the adamantane carboxylic acid derivative, thereby obtaining the adamantane amine derivative. The preparation method is capable of importing groups of rich types to two C atoms of the adamantane and also capable of constructing adamantane amine molecules diversified in structure on the two C atoms.