100 results about "Cyclobutanone" patented technology

This invention provides cholesterol absorption inhibitors of Formula I:and the pharmaceutically acceptable salts thereof, wherein R12 is an alkyl, alkeny or alkynyl group mono- or poly-substituted with —OH, —COOH or a combination of—OH and —COOH, and R9 contains an alkyl, alkeny or alkynyl group substituted with a heterocyclic ring, amino or sulfonyl. The compounds are useful for lowering plasma cholesterol levels, particularly LDL cholesterol, and for treating atherosclerosis and preventing atherosclerotic disease events.

The invention discloses a synthesis method of oxetanone. The method comprises the steps: in an organic solvent and in the presence of a catalyst, a halide and an alkali, utilizing an oxidant to oxidize oxetanol, and then separating and purifying to obtain oxetanone. The method adopts the organic oxidation system for oxidation production of oxetanone for the first time, is cheap in adopted materials and simple in operation, avoids use of methyl azide, butyl lithium, or 1,3-dichloroacetone and other dangerous chemicals, enables the synthesis method of oxetanone to be safely amplified, and can be produced in large scale; the method is friendly to the environment and avoids use of phosphorus pentoxide and other reagents, so that the process meets the requirements of environmental protection; and moreover, the method increases the reaction yield which is increased from 50% to 80% or more, thereby greatly reducing the production cost, and being in favor of further application and development of oxetanone in organic chemistry and biological medicines.

The invention discloses a single-component polyurea coating. Cyclobutanone is used as a cosolvent and a closing agent at the same time; terminating amino of amino-terminated polyoxypropylene ether is subjected to chemical closing; an intermediate (ketoimine) obtained after closure and a component containing -NCO cannot generate a chemical reaction in a condition of air (moisture) isolation, and can coexist in the same system; the mixture of the intermediate (ketoimine) is subjected to closure relief under the action of moisture once being in contact with air; the terminating amino is released; amino-NH2 quickly generates a reaction with the -NCO, so as to form a urea bond. The single-component polyurea coating has excellent physicochemical properties of higher mechanical properties, wear resistance, wet skid prevention, corrosion prevention and the like, is less influenced by solvents (acetone, ethylene glycol and the like), and can adapt to an environment of which the content of an organic solvent is high or the concentration of engine oil is higher. The single-component polyurea coating provided by the invention has the advantage that a preparation method is simple, and is suitable for industrialized production.

The invention belongs to the field of cephalosporin antibiotic medicaments, and in particular relates to a method for synthesizing 7-phenylacetylamino-3-chloromethyl cephalosporin alkyl acid p-methoxybenzyl ester (GCLE). The technical proposal is that the method comprises the following steps: reacting penicillin sulfoxide ester with ammonium benzene sulfinate and 2-mercaptobenzothiazole in dichloromethane, and steaming out a solvent at normal pressure to generate aza-cyclobutanone thiosulfinate intermediate; adding dichloromethane to the intermediate after cooling, stirring and introducing saturated brine ice for cooling, adding trichloro isocyanic acid for reaction so as to generate an allylic chlorination product of the aza-cyclobutanone thiosulfinate; and reducing the pressure and drying the allylic chlorination product by distillation, adding dimethyl formamide to the product, stirring and introducing saturated brine ice for cooling, adding ammonia for reaction, adding water and dichloromethane to the mixture, mixing and stirring the mixture, standing for layering, transferring a dichloromethane layer at the bottom layer to another reactor, and steaming out the solvent at the normal pressure to obtain a dry product which is the GCLE. The method has the advantages of mild reaction condition, few reaction steps, simple operation, short production cycle, and improved production efficiency.

The present invention relates to a cost effective and industrially advantageous process for the preparation of (3R,4S)-1-(4-Fluorophenyl)-3-[3(S)-3-(4-fluorophenyl)-3-hydroxypropyl)]-4-(4-hydroxyphenyl)-2-azetidinone, referred to here as Ezetimibe, it is represented as formula (1).

The invention discloses a method for detecting radiolysis products(2-dodecyl cyclobutanone); the method includes the following steps that: radiating samples are put in a chromatography column using silica gels as fillers, and the normal hexane is used as the first-part eluant for eluting neutral hydrocarbon impurities; the normal hexane solution in which the volume percent of the ether is 1 to 2 percent is used as the second-part eluant for eluting the 2-dodecyl cyclobutanone, and the eluent of the second-part eluant containing the 2-dodecyl cyclobutanone is recovered, and then the content of the 2-dodecyl cyclobutanone is measured. The method of the invention utilizes the separation and extraction of the silicon gel chromatography column and the air-mass combination quantitative analysis to detect the 2-DCB, thereby the separation effect of the 2-DCB in the radiating samples is good, and the detection limit, the precision and the rate of recovery all meet requirements on the analysis and detection of the radiating samples. Compared with the EN1785 method, the method of the invention has the advantages of high extracting efficiency, big carrying capacity of samples, low detection limit and low cost, etc.

The invention relates to a purifying process of cyclobutanone, and aims to provide the purifying process of cyclobutanone simple in method, lower in cost and applicable to industrial production. The purifying process of cyclobutanone comprises the following steps: adding a metal oxidant into a cyclobutanone crude product, and stirring to react for 2-24 hours; rectifying at normal pressure, and collecting fractions at 98-99 DEG C to obtain the product. The purifying process of cyclobutanone provided by the invention has the following advantages that in the whole method, the metal oxidant is just added to stir and react, and the metal oxidant is lowvery cheap in price and is solid at normal temperature and is easy to be separated from organic phases; the whole reaction is not high in temperature (does not exceed 40 DEG C), low in energy consumption and relatively mild in condition of removing impurities; the process can be carried out under a condition of room temperature, so that the process is very applicable to industrial production; the whole process flow is very simple and the purity of cyclobutanone prepared is over 98%.

The present invention relates to a 2-tertbutyloxycarbonyl-7-carbonyl-5-O-2-spiro(3.4)octane synthesis method. A purpose of the present invention is mainly to solve the technical problems of high price of the reagent used in the existing synthesis route, high risk and no suitability for industrial production. According to the present invention, the three-step method is used to synthesize, wherein the first step is that a saturated ammonium chloride aqueous solution of zinc powder is added to a tetrahydrofuran solution of 1-tertbutyloxycarbonyl-3-azetidinone, then allyl bromide is added in a dropwise manner, and the reaction solution reacts at a room temperature overnight to obtain 1-tertbutyloxycarbonyl-3-allyl-azetidinol, the step is that an aqueous solution of sodium hydrogen sulfite is added to an acetonitrile aqueous solution of the 1-tertbutyloxycarbonyl-3-allyl-azetidinol and sodium periodate, and stirring is performed for 16 h at a temperature of 80 DEG C to obtain 2-tertbutyloxycarbonyl-7-hydroxy-5-O-2-azaspiro(3.4)octane, and the third step is that pyridinium chlorochromate is added to a dichloromethane solution of the 2-tertbutyloxycarbonyl-7-hydroxy-5-O-2-azaspiro(3.4)octane under ice bath, and a reaction is performed at a room temperature overnight to obtain the 2-tertbutyloxycarbonyl-7-carbonyl-5-O-2-spiro(3.4)octane.

The invention discloses a synthesis method of a pyrrole [1, 2-a] quinoline derivative, and the method is as follows: dissolving a 3-amino cyclobutanone compound and an alpha-halogenated acetylene as starting materials in an organic solvent for reaction in the presence of an alkaline catalyst, monitoring reaction process by TLC, after the reaction, cooling to room temperature, adding saturated salt water to the reaction system, using an extraction agent for extraction until the water phase is clarified, combining organic phases, drying the organic phases with a drying agent, filtering, concentrating, and performing column chromatography to obtain the pyrrole [1, 2-a] quinoline derivative. The poly nitrogen-containing fused-heterocyclic pyrrole [1, 2-a] quinoline derivative with a highly-complex structure can be synthesized by one step without intermediate separation, the reaction raw materials are easy to obtain, and the synthesis method has the advantages of convenient operation, high product yield and more convenient synthesis process, shortens the reaction process and reduces the reaction time.

The invention relates to a method for synthesizing 3-(Boc-aminomethyl)cyclobutanone. The method for synthesizing 3-(Boc-aminomethyl)cyclobutanone provided by the invention mainly solves the technicalproblems of high raw material cost and relatively difficult post-processing according to the existing synthesis method. The method for synthesizing 3-(Boc-aminomethyl)cyclobutanone provided by the invention comprises the following steps: 3-oxocyclobutanecarboxylic acid and trimethyl orthoformate are reacted in the methanol solution to generate a compound 1; the compound 1 and benzylamine are reacted in the methanol solution under an action of sodium methoxide to generate a compound 2; the compound 2 and sodium bis(2-methoxyethoxy)aluminiumhydride are reacted in tetrahydrofuran solution to generate a compound 3; the compound 3 is subjected to a Pd / C debenzylation and hydrogenation operation in the methanol solution to obtain a compound 4; the compound 4 and Boc2O are reacted in the methanolsolution to obtain a compound 5; the compound 5 is reacted in a 0.05 M hydrochloric acid solution generate a target compound 6. By performing an enzymatic catalyzed deglandulation action of on the corresponding prochiral 3-substituted cyclobutanone, a series of gamma-butyrolactone derivatives, including some spiro derivatives, can be obtained; and all the derivatives are inhibitors having good biological activity.

The invention discloses a novel method for preparing an ezetimibe key intermediate, which uses an intermediate (II) as a raw material. The intermediate (II) is directly reacted with a 4-fluorine phenyl grignard reagent under effects of alkali, and the key intermediate (3R and 4S)-1-(4-fluorine phenyl)-3-[3-(4-fluorine phenyl)-3-oxo propyl group]-4-substituted phenoxy-2-nitrogen heterocyclic cyclobutanone (I) is obtained by one step. Compared with the existing synthetic route, the method shortens three steps of reaction, does not use a zinc reagent or a palladium catalytic agent, and greatly saves cost of industrial production. By means of the method, processing is simple, purification is convenient, one-step yield can achieve more than 60%, and the novel method has great industrialization production prospects.

During the chlorination of dithioaza cyclobutanone derivative, dithioaza cyclobutanone derivative is first dissolved in some solvent and glacial acetic acid is added to the solution through stirring,and sodium hypochlorite or potassium hypochlorite is then added into the solution to react at 0 deg.c for 2 hr. After finishing reaction, water layer is separated from the reacted liquid, the organicmatter layer is washed with table salt solution, dried with anhydrous sodium sulfate, filtered to obtain filtrate, and the filtrate is vacuum evaporated to eliminate solvent and to obtain yellow ropyliquid of the required chloride. The method of the present invention has mild technological conditions and less environmental pollution and is suitable for industrial production.

The invention discloses a preparation method of 3-aminomethyl oxetane and its oxalate and acetate, mainly solving the problem of existing preparation method is not suitable for large scale production. The method disclosed herein is characterized by using 3-oxacyclobutanone as a starting material, reacting the starting material with nitromethane in alkali condition with the effect of methanesulfuryl chloride to obtain 3-(nitromethylene)oxetane; then under the effect of activated carbon supported palladium hydroxide and hydrogen, reducing to obtain 3-aminomethyl oxetane, and then reacting with oxalic acid or acetic acid to form salts. The total yield is 51%.

The invention discloses a method for synthesizing a 4-cyclobutyl biphenyl fluorine-containing compound. The method comprises the following steps: by taking chlorine benzene halide as an initial raw material, performing a Grignard reaction; performing a coupling reaction on the chlorine benzene halide with cyclobutanone so as to generate cyclobutanol chlorobenzene; performing a dehydration reactionso as to generate cyclobutene chlorobenzene; performing a one-pot method reaction to generate 4-cyclobutene phenylboronic acid; performing a coupling reaction with fluorine-containing benzene halideso as to generate a 4-cyclobutene biphenyl fluorine-containing compound; performing a hydrogenation reaction, thereby obtaining a 4-cyclobutyl biphenyl fluorine-containing compound IX. The method hasthe characteristics of being high in conversion rate, low in cost, safe and stable in process, short in reaction step, green and environmental-friendly in process route and small in pollutant emission.

The invention discloses a method for synthesizing cyanoalkoxy substituted tetra-substituted olefin derivatives with potential biological activity. According to the method, 3,3-dialkylthio-2-propylene-1-ketone and cyclobutanone oxime ester, which are easy to prepare and have structural diversity and multiple reaction centers, are used as raw materials, so that the free radicals are generated through cyclobutanone oxime ester to carry out olefin addition, and the cyanoalkoxy substituted tetra-substituted olefin derivative is generated in one step. The method has the advantages of easily available raw materials, simple operation, mild synthesis reaction conditions, high reaction efficiency, and diversity of functional groups.

The invention discloses a method of assisting to identify irradiated lipid-containing foods. The method comprises the steps of: (1) sequentially connecting a biotinylated epsilon subunit clonal antibody, streptavidin and a biotinylated 2-dodecyl cyclobutanone polyclonal antibody on epsilon subunit of F0F1-ATP (Adenosine Triphosphate) synthase to obtain a molecular motor biosensor; (2) extracting lipid-containing foods which are not irradiated by using a solvent to obtain a solvent extracting solution a, carrying out reaction on the solvent extracting solution a and the molecular motor biosensor under the condition with the existence of a start buffer solution, adding a PBS (Phosphate Buffer Solution) into a reaction system to stop the reaction, uniformly mixing a reaction solution of the reaction system and a fluorescein / luciferase solution, and detecting a mixture by using an ultra-weak luminescence instrument to obtain the fluorescence intensity of the lipid-containing foods which are not irradiated; and (3) extracting the lipid-containing foods to be identified by using a solvent to obtain a solvent extracting solution b, and carrying out the same operations in the step (2) on the solvent extracting solution b to obtain the fluorescence intensity of the lipid-containing foods to be identified, thus realizing identification of the lipid-containing foods. With the adoption of the method of identifying the irradiated lipid-containing foods, the detection time can be shortened to be about 10mins, and in addition, the detection sensitivity of 2-DCB (Dodecyl Cyclobutanone) can reach 10-4 micrograms / mL, thus satisfying the existing detection range of the irradiated lipid-containing foods.

The invention discloses a synthesis strategy for constructing a 2-cyanoalkyl sulfonyl substituted 3,4-dihydronaphthalene compound by taking MCPs, a cyclobutanone oxime ester compound and K2S2O5 as rawmaterials through visible light catalysis, wherein two carbon-carbon sigma bonds are broken in a one-pot reaction to form a carbon-carbon bond and two carbon-sulfur bonds. According to the invention,cyanoalkyl free radicals are formed to capture SO2, and subsequently sulfonyl free radicals are formed to carry out ring-opening and cyclizing on MCPs; and the synthesis method disclosed by the invention has the advantages of mild reaction conditions, simplicity, high efficiency, easily available raw material sources, wide substrate application range and high target product yield.

The invention discloses a method for synthesizing a cyanoalkyl substituted tetra-substituted olefin derivative with potential biological activity. According to the method, 3,3-dialkylthio-2-propylene-1-one and cyclobutanone oxime ester which are easy to prepare and have structural diversity and multiple reaction centers are used as raw materials, free radicals are generated through cyclobutanone oxime ester to carry out olefin addition, and the cyanoalkyl-substituted tetra-substituted olefin derivative is generated in one step. The method has the advantages of easily available raw materials, simple operation, mild synthesis reaction conditions, high reaction efficiency, and diversity of functional groups.

The invention provides a synthesis method of cyclobutanone. The method taking cyclopropanecarboxylic acid as a raw material comprises the following steps: reducing the raw material into cyclopropylmethanol, rearranging the cyclopropylmethanol under an acidic condition to obtain cyclobutanol, and carrying out TEMPO oxidation to obtain cyclobutanone. The method has the following advantages: the rawmaterials are cheap, the operation is simple, the total yield is high, and the product with the purity of 99% can be obtained through simple post-treatment. The method produces less three wastes and is suitable for large-scale production.

The invention belongs to the fields of organic synthesis and medicine synthesis, and especially relates to a synthesis method of 3-oxetane acetic acid. The synthesis method includes the following steps: (1) performing a reaction to 3-oxetanone and benzyloxycarbonylmethylene triphenylphosphine to obtain an intermediate product 2-(oxetane-3-yl-methylene)benzyl acetate; (2) performing hydrogenation debenzylation to the 2-(oxetane-3-yl-methylene)benzyl acetate to obtain the final product 3-oxetane acetic acid. The reactions in the method can be carried out just at room temperature and reaction conditions are easy to control. The final product can be obtained through re-crystallization and purification, so that the product is high in purity, and deterioration of the product during purification is avoided. The method has reasonable route design, simple process, high yield and short synthesis period, and can provide a high-purity raw material for a subsequent synthesis reaction sufficiently and timely.

A salt-free process for preparing cyclobutanone, including isomerizing cyclopropylmethanol, preferably in aqueous solution, in the presence of an acidic heterogeneous catalyst to form cyclobutanol and, preferably after extraction and removal of the extractant, dehydrogenating the cyclobutanol over a heterogeneous catalyst.

The invention discloses a preparation method of an intermediate compound for synthesizing briracetam, the intermediate compound is (R)-4-propyl-dihydrofuran-2-ketone, the preparation method comprises the following steps: 3-propyl cyclobutanone is subjected to asymmetric Baeyer-Villiger oxidation reaction in the presence of a catalyst and an optional oxidant, and the intermediate compound is (R)-4-propyl-dihydrofuran-2-ketone. And the (R)-4-propyl-dihydrofuran-2-one is obtained through a reaction. The invention further discloses a preparation method of the briracetam, wherein the intermediate compound (R)-4-propyl-dihydrofuran-2-ketone is prepared by the preparation method of the intermediate compound, and then the intermediate compound (R)-4-propyl-dihydrofuran-2-ketone reacts with L-2-aminobutanamide to obtain the briracetam. The method is simple in route, short in step, low in cost, safe and high in product yield and chiral purity.

The invention belongs to the technical field of fine chemical engineering, and relates to a preparation method and application of a metal organic cage compound. According to the preparation method, Zn<2+> in transition metal salt is used as a node, L is used as a ligand, and a reaction is conducted to prepare the metal organic cage compound; a synthetic route is that Zn<2+> and L produce Zn-L; theligand L is H<2>ZPA; and the transition metal salt is one selected from a group consisting of zinc perchlorate, zinc nitrate, zinc tetrafluoroborate and zinc trifluoromethanesulfonate. The metal organic cage compound prepared by using the method is low in raw material price, high in yield, stable in chemical property, easy to put into practical application, and capable of efficiently catalyzing cyclobutanone to prepare butyrolactone and catalyzing selective oxidation of thioether to prepare sulfoxide under the condition of mild illumination.

The invention relates to a method for chloridizing a nitrogen heterocyclic cyclobutanone isobutene derivant. The method has mild process condition, stable reaction, available materials; dilute chlorine is adopted for chlorination and has high chlorination selectivity and high yield; the reaction solvent is a non-phenoxin solvent, has no limitation of environmental protection, high reclaiming rate, little environmental pollution and rapid reaction and can improve production efficiency; the raw materials are common industrial products and are cheap and available; and the method is in particular suitable for production in chemical industry and medical industry and is suitable for middle- and small-scale production.

The invention provides a 3-oxetanone synthesis method, which comprises: removing the protection group from an intermediate in an organic solvent I by using an organic strong acid, neutralizing with aweak alkali to achieve an alkaline pH value, carrying out concentration distillation on the solvent to obtain a oxetan-3-ol crude product, oxidizing the oxetan-3-ol with an oxidizing agent in the presence of a catalyst I, a halide and an alkali, and carrying out separating purification to obtain the 3-oxetanone product, wherein the intermediate preparation method comprises: carrying out a ring opening reaction by using epichlorohydrin and glacial acetic acid as raw materials under the catalysis of a catalyst II, adding ethyl vinyl ether under an organic strong acid condition, carrying out a protection group forming reaction, and carrying out a ring formation reaction under a strong alkali condition so as to obtain the key intermediate solution. According to the present invention, the oxetan-3-ol preparation process is combined without the purifying of oxetan-3-ol so as to eliminate the oxetan-3-ol purifying step; and the method has characteristics of inexpensive raw materials, short route, no use of dangerous reagents and the like.

The invention provides a novel method for synthesizing an optically-pure sulfur-containing quaternary heterocyclic drug intermediate which is (S)-2-[(tert-butyloxycarboryl)-amino]-2-[3-(3-methoxy)-1-cyclopropylsulfonyl]-acetic acid. The method comprises the following steps: taking thietanone as a starting raw material, carrying out Wittig-horner reaction, methoxylation, oxidization and enzymatic catalysis hydrolytic resolution to prepare an optically-pure target compound. The method is easily available in raw materials, simple in requirements on equipment and efficient in synthesis of chiral compounds; the steps can be enlarged to kilogram scale for production; the method is a novel method suitable for industrial application.