146 results about "Trimethyl orthoformate" patented technology

The present invention relates to a new industrial process for the synthesis of solvate- free 17a-acetoxy-11ss-[4-(N,N-dimethyl-amino)-phenyl]-19-norpregna-4,9-diene-3,20-dione [CDB -2914] of formula (I) which is a strong antiprogestogene and antiglucocorticoid agent. The invention also relates to compounds of formula (VII) and (VIII) used as intermediates in the process. The process according to the invention is the following: i) 3-(ethylene-dioxy)-estra-5(10),9(11)-diene-17-one of formula (X) is reacted with potassium acetilyde formed in situ in dry tetrahydrofuran by known method, ii) the obtained 3-(ethylene-dioxy)-17a-ethynyl-17ss-hydroxy-estra-5(10),9(11)-diene of formula (IX) is reacted with phenylsulfenyl chloride in dichloromethane in the presence of triethylamine and acetic acid, iii) the obtained isomeric mixture of 3-(ethylene-dioxy)-21-(phenyl-sulfinyl)-19-norpregna-5(10),9(11),17(20),20-tetraene of formula (VIII) is reacted first with sodium methoxide in methanol, then with trimethyl phosphite, iv) the obtained 3-(ethylene-dioxy)-17a-hydroxy-20-methoxy-19-norpregna-5(10),9(11),20-triene of formula (VII) is reacted with hydrogen chloride in methanol, then v) the obtained 3-(ethylene-dioxy)-17a-hydroxy-19-norpregna-5(10),9(11l); -diene-20- one of formula (VI) is reacted with ethylene glycol hi dichloromethane in the presence of trimethyl orthoformate and p-toluenesulfonic acid by known method, vi) the obtained 3,3,20,20-bis(ethylene-dioxy)-17a-hydroxy-19-norpregna- 5(10),9(11)-diene of formula (V) is reacted with hydrogen peroxide in a mixture of pyridine and dichloromethane in the presence of hexachloroacetone by known method, vii) the obtained 3,3,20,20-bis(ethylene-dioxy)-17a-hydroxy-5,10-epoxy-19-norpregn-9(11)-ene of formula (IV), containing approximately a 1:1 mixture of 5a,10a- and 5ss,10ss-epoxides, is isolated from the solution and reacted with a Grignard reagent obtained from 4-bromo-N,N-dimethyl-aniline in tetrahydrofuran.

The invention relates to a preparation method of an azoxystrobin intermediate. The method comprises the following steps of: (1) synthesizing benzofuranone from o-hydroxyphenylacetic acid serving as a raw material; and (2) making benzofuranone react with trimethyl orthoformate to generate the azoxystrobin intermediate, wherein no solvent is used in the reaction in the step (1); and the reaction isperformed by the following steps of: putting o-hydroxyphenylacetic acid and 0-3 percent of catalyst into a reaction kettle; preserving heat in vacuum at the temperature 125-180 DEG C to react for 2-3hours; and evaporating water generated by the reaction in vacuum, wherein the residue in the reaction kettle is benzofuranone. The method has the advantages of simple process, high yield of the azoxystrobin intermediate and low production cost.

The invention relates to a simple and quick method for synthesizing an improved vitamin B1 intermediate 2-methyl-4-amino-5-aminomethylpyrimidine. The method comprises the following steps: condensing 3-alkyl (aryl) formamido-propionitrile serving as a raw material with acetamidine in the catalytic action of lewis acid; cyclizing with trimethyl orthoformate, and hydrolyzing under an alkaline condition to prepare the vitamin B1 key intermediate 2-methyl-4-amino-5-aminomethylpyrimidine. The four reacting processes are performed in sequence by a one-pot reaction, and the product in each step does not need to be separated and purified. According to the method, highly carcinogenic o-chloroaniline or other small molecular aniline compounds are not used, residues of o-chloroaniline compounds in the vitamin B1 product can be eliminated. Furthermore, the preparation process is short and convenient in flow, small in wastewater amount and high in yield.

The invention discloses a method for synthesizing phenetyl, which uses p-chlorophehol or p-bromophenol as starting reaction raw material. It first uses methyl, benzyl or tert-butyl to protect the phenolic hydroxyl, the parivis which is protected by the phenolic hydroxyl reacts with the magnesium in the ether, tetrahydrofuran, tert-butyl methyl ether, isopropyl ether and its mixing solution to obtain the Grignard reagent, the Grignard reagent directly reacted with the etox to obtain the tyrosol which is protected by the phenolic hydroxyl, the tyrosol reacts with the dimethyl sulfate, dimethyl carbonate, trimethyl orthoformate to obtain the tyrosol ether which is protected by phenolic hydroxyl, which obtains the product in acid or hydrogenation protection.

The invention discloses a method for preparing progesterone by taking 1,4-androstenedione as a raw material, which comprises the following steps: 1) dissolving 1,4-androstenedione into an organic solvent, adding the acid of trimethyl orthoformate or triethyl orthoformate, and introducing nitrogen to protect the 1,4-androstenedione to synthesize the enol ether of 1,4-androstenedione, namely 3-methoxy-androstane 3,5-diene-20-ketone; and 2) dispersing (1-methoxy ethyl)-triphenylphosphine salt in a reaction medium, an organic solvent, adding alkali at low temperature, performing a Wittig reaction of the 3-methoxy-androstane 3,5-diene-20-ketone synthesized in the step 1), and purifying and crystallizing to obtain progesterone. By adopting the 1,4-androstenedione as the raw material, the method solves the problem that of lack in raw materials for synthesizing steroid drugs such as progesterone, and improves the utilization rate of 1,4-androstenedione and the yield of progesterone; the preparation process is simple.

The invention relates to a preparation method of high-purity palbociclib. The method comprises using acetoacetate for reflux dehydration in the function of an acid catalyst to prepare 2-acetyl-3-methyl-2-diethyl (methyl) glutaconate (III), condensing the compound (III) and trimethyl orthoformate for methanol removal to obtain 2-acetyl-3-methyl-4-methoxymethylene-2-diethyl (methyl) glutaconate (IV), cyclizing the compound (IV) and N-(5-(4-tertbutoxycarbonyl-1-hexahydropiperazinyl)-2-pyridyl) guanidine (V) with pyrimidine to obtain 2-acetyl-3-[[5-(4-tertbutoxycarbonylpiperazinyl-1-yl) pyridine-2-yl] amino]-3H-4-one-dihydropiperazinyl-2-ethyl (methyl) butenyl ester (VI), and finally cyclizing the compound (VI) and cyclopentylamine to remove Boc protecting groups, thereby obtaining palbociclib. The preparation method is cheap and available in raw materials, short in technical process, simple and convenient to operate, good in reaction selectivity, and high in product yield and purity and is green and eco-friendly.

A lappaconitine acetal derivative with antineoplastic activity and a synthetic method thereof are disclosed. By using lappaconitine and an aromatic aldehyde derivative as raw materials, an unreportedlappaconitine acetal derivative is synthesized under catalysis of phospho-tungstic acid and trimethyl orthoformate. The synthetic method of the lappaconitine acetal compound has high operational safety and mild reaction conditions, and is suitable for industrial production. It shows through preliminary biological activity tests that the compound has good antineoplastic activity and can be used inthe research on antineoplastic drugs.

Disclosed are high-quality trimethyl orthoformate and a preparation method of the trimethyl orthoformate. The preparation method of the trimethyl orthoformate comprises the steps of obtaining amine salt by reaction between hydrocyanic acid and carbinol and hydrogen chloride and obtaining a trimethyl orthoformate coarse product through alcoholysis; and carrying out centrifugal separation on alcoholysis reaction liquid, and refining the obtained coarse product by adding aqueous alkali. The purity of the trimethyl orthoformate product obtained with the refining method can reach to 99.6%-99.8wt%, triazine impurity content is pretty small and is only 0.001-0.06%, and particularly purification yield of the refining method is more than 90% and can reach to 96% to the maximum degree. According to the trimethyl orthoformate and the preparation method of the trimethyl orthoformate, treating agents can be obtained easily, cost is low, reaction condition is moderate, and the trimethyl orthoformate and the preparation method of the trimethyl orthoformate are particularly suitable for industrial mass production.

The invention discloses a preparation method of a polyalcohol acetal compound. The preparation method comprises the following steps that polyalcohol, a solvent, a catalyst, a promoter and a water absorbent are added in a reaction vessel and stirred for 10-30 minutes, then substituted aldehyde is added into the mixture to be subjected to a reaction for 2-36 hours at the room temperature, stirring is conducted for 10-30 minutes after water is added, suction filtration, washing and swab-off are conducted, and the polyalcohol acetal compound is obtained, wherein polyalcohol is sorbitol, xylitol ormannitol, the solvent is dimethyl sulfoxide or a compound of dimethyl sulfoxide and methyl alcohol, the catalyst is sulfuric acid, hydrochloric acid, phosphoric acid or nitric acid, the promoter is phosphotungstic acid, the water absorbent is trimethyl orthoformate or triethyl orthoformate, and the substituted aldehyde is aromatic aldehyde or fatty aldehyde. The method is novel in route design, the reaction raw materials are easy to obtain, the product purity is good, post-treatment is simple, the applicability is high, and the method can be widely applied to synthesis of polyalcohol diacetaland polyalcohol triacetal compounds with different structures.

The invention relates to a production process for synthesizing 9-cyclo-hexadecylene lactone, which comprises the following steps: (1) putting aleuritic acid and trimethyl orthoformate into a reactor according to weight ratio of between 1 to 0.5 and 1 to 4, and heating up the mixture to raise the temperature to finish a deshydroxy polyreaction at a temperature of between 60 and 180 DEG C; and (2) adding a depolymerization catalyst into the mixture to perform a depolymerization cyclization reaction under vacuum condition at a temperature of between 180 and 240 DEG C to generate the product of the 9-cyclo-hexadecylene lactone which is distilled out through adding an azeotropic agent to perform continuous azeotropic azeotropy, and rectifying and refining the distilled product to obtain the finished product of the 9-cyclo-hexadecylene lactone. The production process has the advantages that catalysts such as proton acid, low-carbon alkyl anhydride and the like are not used so that the cost is reduced, washing wastewater treatment processes are reduced, and no environmental pollution is caused; and the complex reaction processes are finished through simple process steps in a reaction pot, so that the operation is greatly simplified, and the industrial production is achieved.

The invention belongs to the technical field of trimethyl orthoformate, and discloses a synthesis technology of trimethyl orthoformate. The technology comprises the following steps: 1, proportioning; 2, crystallization salt formation, and alcoholysis; and 3, distillation. The synthesis technology has the advantages of good environmental protection property, energy saving, emission reduction, realization of large-scale industrial production, and high purity of the synthesized product.

The invention discloses a synthesis method of 2, 9-substituted 4-halogenated-1, 10-phenanthroline, and belongs to the technical field of organic synthesis. The synthesis method comprises the followingsteps: S1, coupling mimic acid and trimethyl orthoformate to form alkene; S2, reacting a 8-aminoquinoline derivative with an intermediate alkene in the first step to generate secondary amine; S3, allowing secondary amine to be subjected to intramolecular cyclization to prepare a phenanthroline derivative of 4-keto carbonyl; and S4, synthesizing 4-halogenated-1, 10-phenanthroline of which the 2, 9positions are substituted through halogenation of phosphorus oxyhalide. According to the method, a four-step synthesis method is adopted, all the raw materials are strictly fed in sequence, corresponding purification treatment is carried out after each step of reaction, the conversion rate of each step of reaction is increased, finally, the yield of the product is effectively increased, and the problems that an existing synthesis method is difficult to synthesize and purify through adoption of a one-pot method, and the yield is low are solved; and the purification process is simple, generation of a large amount of waste acid is avoided, environment friendliness is achieved, and industrial production is facilitated.

The present invention provides a preparation method of 1-methyl-4-(2-methyl-2H-tetrazole-5-yl)1H-pyrazole-5-sulfamide. The preparation method comprises that trimethyl orthoformate and malononitrile are adopted as starting raw materials, a three-step reaction is performed to obtain 1-methyl-5-amino-4-(tetrazole-5-yl)pyrazole, the 1-methyl-5-amino-4-(tetrazole-5-yl)pyrazole reacts with dimethylsulfate in the presence of an acid-binding agent to obtain 2-methyl-5-(1-methyl-5-amino-1H-pyrazole-4-yl)-2H-tetrazole, the 2-methyl-5-(1-methyl-5-amino-1H-pyrazole-4-yl)-2H-tetrazole is subjected to a sodium nitrite diazo-reaction under an acid condition, the obtained material reacts with a sodium sulfite-copper chloride-acetic acid mixture, and finally hydrolysis with ammonia is performed to obtain the target product. The present invention further provides a preparation method of azimsulfuron prepared from the 1-methyl-4-(2-methyl-2H-tetrazole-5-yl)1H-pyrazole-5-sulfamide. The preparation method of the present invention has characteristics of short reaction route, environmental protection raw materials, and high yield.

The invention discloses a method for preparing known impurities of gefitinib, comprising: mixing initial raw materials: 2-amino-4-methoxy-5-(3-morpholine propanolato) cyanophenyl, 3-fluorine-4-chloroaniline and acetate solvent with trimethyl orthoformate or triethyl orthoformate, simply preparing a crude product of the impurities of gefitinib, and recrystallizing to obtain the high purity known impurities of gefitinib, that is N-(4-chloro-3-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine. The method has advantages of short synthesis route, simple operation, and high purity of obtained product, and can be used for reference substance research.

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 method for synthesizing 2-amino-6-chloropurine, and belongs to the field of organic chemical synthesis. The synthesis method of the 2-amino-6-chloropurine comprises the following steps: enabling 6-hydroxyl-2,4,5-triaminopyrimidine to react with trimethyl orthoformate to generate guanine, and enabling the guanine to react with hydrogen chloride and hydrogen peroxide to generate 2-amino-6-chloropurine. The method has the advantages of short reaction time, high yield, no generation of a large amount of three wastes, simple operation, and facilitation of industrial production.

The invention discloses a one-pot method used for synthesis of diaryl methyl ketal. The on-pot method is shorter in process, and is more effective. A novel synthesis strategy is provided for synthesisof some complex diaryl ketones. According to the one-pot method, an aryl carboxylic acid and a R-substituted benzene compound are selected, in the presence of trifluoroactic anhydride, boron trifluoride diethyl etherate is taken as a catalyst, direct acylation reaction is carried out, without treatment, methanol and trimethyl orthoformate are added for continuous reaction so as to obtain a diarylmethyl ketal product, so that one-pot synthesis of diaryl methyl ketal from aromatic acids is realized.

The invention discloses a preparation method of neohesperidin dihydrochalcone. The method comprises the following steps: (1) carbonyl protection: dissolving the neohesperidin in an organic solvent or organic solvent aqueous solution, adding trimethyl orthoformate or triethyl orthoformate and ketal catalyst to perform the ketal reaction, reducing pressure and concentrating, cooling and crystallizing, filtering and drying to obtain a compound I; (2) hydrolysis reaction: dissolving the compound I in an aqueous alkali of the compound II; (3) hydrogenation reaction: adding the hydrogenation catalyst, introducing nitrogen to protect, and introducing the hydrogen to perform the hydrogenation reaction, filtering to obtain the aqueous alkali of the compound III; (4) acidification and crystallization: regulating pH value, cooling and crystallizing, filtering and drying to obtain the neohesperidin dihydrochalcone. The yield of the neohesperidin dihydrochalcone prepared through the method disclosed by the invention could reach 97.2%, the purity can reach 98.5%. The method disclosed by the invention is simple, mild in reaction condition and low in cost, and is capable of partially recycling the catalyst and suitable for the industrial production.

The invention provides a synthetic technology of azoxystrobin. The synthetic technology mainly comprises the following steps: adding hydroxy benzene acetic acid and trimethyl orthoformate butyl anhydride in a reaction still, and carrying out a heat preservation reaction for 20 hours; obtaining a kind of black solid through vacuum concentration, and recrystallizing after dissolving the black solid by using methyl alcohol; pumping nitrogen for protection, then adding 4,6-dichloro pyrimidine and methyl formate, slowly and dropwise adding a sodium methylate solution, and distilling after a reaction is ended, thus obtaining a residue mixture; adding a potassium hydroxide aqueous solution, reducing the temperature, standing after adding methylbenzene, separating an organic phase and a water phase, adding KHSO4 after desolventizing the organic phase, obtaining grease after the reaction is carried out by rising the temperature, continuously adding 2-cyano phenol and potassium carbonate, and cooling after the reaction; adding the methyl alcohol, recrystallizing after cooling a system to 0 DEG C, and obtaining the azoxystrobin after filtering and drying. Compared with the prior art, the synthetic technology disclosed by the invention has the advantages that the method is simple, raw materials are cheap and easy to obtain, the environment pollution is small, the yield of the azoxystrobin is high, and the industry prospect is good.

The invention discloses a method for preparing a compound of the following formula (II) by reacting benzofuranone compounds with trimethyl orthoformate, wherein R ¹ , R ² , R ³ and R ⁴ The definition is the same as that in the description.

The invention discloses a synthetic method for an azoxystrobin intermediate. The method comprises the following steps: firstly, benzofuranone, trimethyl orthoformate and acetic anhydride are used as raw materials, reactive distillation operation is performed, and thus condensation substances are obtained by a one-pot method with a high yield; and secondly, a one-pot method reaction is performed on the condensation substances and 2,6-dichloropyrimidine in a methanol solution of sodium methylate; and finally, after the reaction is finished, the acidity is regulated, methanol is recycled, alkali washing is performed, a catalyst of p-toluenesulfonic acid is added to the condensed crude products, a reaction is performed, and thus the azoxystrobin intermediate (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate is obtained. The method is simple in operation, high in yield, less in by-products, and suitable for industrialized production.