51 results about "Formic acid ethyl ester" patented technology

The invention relates to an edoxaban intermediate and a preparation method thereof. The preparation method of the edoxaban intermediate comprises steps as follows: (a), (1s)-3- cyclohexene-1-formic acid is taken as a raw material, and a compound 2 is generated in the presence of a catalyst, a halogen and a weak base; (b), the compound 2 generates a compound 3 under the action of strong base in an absolute ethanol solution; (c), the compound 3 generates a compound 4 in an ammonia and ethanol solution; (d), the compound 4 reacts with a protecting group of amino under the action of a catalyst, and a compound 5, (1S,3R,4R)-3-[(t-butyloxycarboryl)amino]-4-hydroxycyclohexyl ethyl formate, is generated. Raw materials and reagents required in the synthesis method of the edoxaban intermediate are easy to obtain, the yield is high, the cost is low, reaction conditions are mild, three wastes are relatively fewer, and the quality of the product is stable and reliable.

The invention discloses a synthesis method of diethyl azodicarboxylate. The synthesis method comprises the following steps that (1) under the effect of sodium ethoxide, diethyl carbonate and ethyl carbazate are heated for reaction for 1 to 6 hours, the pH of solution is regulated to 3 to 8, white crystals are separated out, the recrystallization is carried out, and hydrogenated diethyl azodicarboxylate is obtained; and (2) the hydrogenated diethyl azodicarboxylate is added at minus 15 DEG C to 45 DEG C, in the acid solution, bromine or hydrobromic acid or sodium bromide and potassium bromide are used as catalysts, excessive hydrogen peroxide is dripped, the reaction is carried out for 1 to 10 hours, the extraction is carried out, organic solvents are removed through distillation, and saffron diethyl azodicarboxylate is obtained. The invention also provides a hydrogenated diethyl azodicarboxylate intermediate and a synthesis method of the hydrogenated diethyl azodicarboxylate intermediate. The synthesis method has the advantages that diethyl carbonate is used as raw materials, cleanness and environment protection are realized, no pollution exists, raw materials can be cyclically utilized, the economy is better, the operation is simple, the reaction temperature range is wide, the reaction is stable, the energy consumption is low, the yield is high, and the industrial production is favorably realized.

The invention discloses a (S)-(((4-methoxy-3,5-dimethyl pyridine-2-yl)methyl)sulfinyl) ethyl thioformate compound, a preparation method of the compound and a process for preparing esomeprazole by using the compound. The compound and the preparation method have the remarkable advantages that: raw materials for synthesis are cheap and can be easily obtained; the reaction conditions are moderate; the yield of the prepared esomeprazole is high; the optical purity is high; the operation is safe; the environment is slightly polluted; and the compound is more suitable for industrial large-scale production.

The invention discloses a method for preparing ethyl (3R,4R,5S)-4,5-epoxy-3-(1-ethyl-propoxy)-1-cyclohexene-1-formate. The preparation method disclosed by the invention comprises the following steps: (a) dissolving ethyl (3R,4R,5R)-3-(1-ethyl-propoxy)-4-hydroxy-5-O-methyl-sulfonyl-1-cyclohexene-1-formate in an alcohol solvent, and carrying out elimination reaction under the effect of ammonia water; and (b) collecting ethyl (3R,4R,5S)-4,5-epoxy-3-(1-ethyl-propoxy)-1-cyclohexene-1-formate from the reaction solution. By using the method disclosed by the invention, the product yield reaches more than 90%, the product purity measured by HPLC (high-performance liquid chromatography) reaches more than 99.5%, and the individual impurity content in the product is less than 0.1%; and the method is suitable for industrial mass production.

The invention discloses a method for synthesis of a tyrosine derivative. The method is a novel method for preparing the tyrosine derivative N-benzoyl-L-tyrosyl-di-n-propylamine. The method mainly solves the problem that the existing synthesis method has a low yield and low product purity. The method realizes the preparation of N-benzoyl-L-tyrosyl-di-n-propylamine by a two-step synthesis technology and comprises the following steps that 1, raw materials of L-tyrosine and benzoyl chloride undergo a reaction in the presence of an inorganic alkali aqueous solution and O,N-(2-benzoyl)-L-tyrosine crystallizes in an acetone aqueous solution; 2, the O,N-(2-benzoyl)-L-tyrosine, triethylamine, ethyl chloroformate and isopropamide are synthesized into O,N-(2-benzoyl)-L-tyrosyl-diisopropylamine in the presence of ethyl acetate; and 3, the O,N-(2-benzoyl)-L-tyrosyl-diisopropylamine is subjected to ethyl acetate extraction and condensation; then benzoyl of an oxy group is removed in an alcohol under alkaline conditions; and acidity adjustment is carried out in an alcohol aqueous solution so that N-benzoyl-L-tyrosyl-di-n-propylamine is obtained. The method is mainly used for preparation of an intermediate of a drug tiropramide hydrochloride from tyrosine as an initial raw material.

The invention discloses a synthesis process of febuxostat. The synthesis process comprises the following steps: taking ethyl 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylate as a raw material to prepare ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5- formate; preparing ethyl 2-(3-formyl-4-isobutoxyphenyl)-4-methylthiazole-5-formate from the ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-formate; preparing ethyl 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-formate from ethyl 2-(3-formyl-4-isobutoxyphenyl)-4-methylthiazole-5-formate; preparing a crude febuxostat product fromethyl 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-formate; and specifically crystallizing the febuxostat crude product to prepare a febuxostat pure product, wherein the febuxostat pure product isa target product. The method solves the problems that an original synthesis route is high in operation risk and not suitable for industrial production.

The invention discloses a method for treating ethyl chloroformate rectifying still residues. The ethyl chloroformate rectifying still residues are further reacted with ethanol, so that ethyl chloroformate in the still residues can be basically reacted completely, the content of diethyl carbonate is increased, the components of the still residues are relatively single, and preparation of high-quality diethyl carbonate is facilitated. The residues subjected to ethanol treatment are subjected to continuous molecular distillation after desolvation and ethanol removal, the system temperature is low, the retention time is short, the heating time of diethyl carbonate is short, and the chromaticity, content, stability and the like of the product are remarkably superior to those of a traditional rectification process. The ethyl chloroformate rectifying still residues are subjected to effective resourceful treatment, high-quality diethyl carbonate is obtained, the amount of three wastes is greatly reduced, and the added value of the product is improved.

The invention relates to a new preparation method of a febuxostat intermediate. The method includes: taking cheap 4-hydroxybenzaldehyde as an initial raw material, firstly preparing aldoxime from 4-hydroxybenzaldehyde and hydroxylamine hydrochloride, then adding a corresponding thio reagent, and preparing a compound 4-hydroxythiobenzamide (152A1-00) by Beckmann rearrangement reaction; utilizing one-pot process, adopting cheap 4-hydroxybenzaldehyde as an initial raw material, carrying out a series of reactions, and then performing cyclization with 2-halogenated ethyl acetoacetate to obtain ethyl 2-(4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylate or different salt forms (152A2x) thereof; and using isobutyl sulfonate (152H1x) with more easily controllable quality to replace bromo-isobutane soas to prepare ethyl 2-(3-formyl-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate (152A4-00). In conclusion, the method provided by the invention is more beneficial to safe, simple and cost-efficientindustrial scale preparation of the febuxostat intermediate with higher purity.

This invention relates to a new method for synthesizing Adapalene 6-[3-(1-King Kong alkyl)-2-naphthoic acid, in which, 2-(1-King Kong alkyl)-4-bromophenyl methyl ether and Zn generate organic Zn reagent in aether-like or non-polarity solvent, which is reacted with 6-bromine-2-naphthoic acid ethyl and analyzed to get the Adapalene.

The invention relates to a method for synthesizing ethyl tetrazole-5-carboxylate, which belongs to the field of organic synthesis and comprises the following steps of: (1) heating and refluxing by taking ethyl cyanoformate and sodium azide as raw materials and a mixed solution of methylbenzene and water as a solvent to generate ethyl tetrazole-5-carboxylate sodium salt; (2) heating and distillingthe reflux liquid obtained in the step (1) to remove methylbenzene; (3) neutralizing the distillate obtained in the step (2) with an acidic solution, and conducting separating to obtain a crude product of ethyl tetrazole-5-carboxylate; and (4) recrystallizing the crude product of ethyl tetrazole-5-carboxylate through a mixed solvent of low-carbon hydrocarbon and water, and conducting separating toobtain ethyl tetrazole-5-carboxylate. The synthesis method disclosed by the invention is simple to operate and high in yield, and the purity of the prepared ethyl tetrazole-5-carboxylate is high.

The invention relates to a preparation and purification method of a key intermediate 4-(1-hydroxy-1-methylethyl)-2-propyl-1-{[2' -(triphenylmethyl-1H-tetrazole-5-yl) (1, 1'-biphenyl)-4-yl] methyl}-1H-imidazole-5-ethyl formate (I) for preparing a chemical drug olmesartan medoxomil for treating hypertension. The invention provides a preparation and purification method for generating a compound (I) by reacting 4-(1-hydroxy-1-methylethyl)-2-propyl-1H-imidazole-5-carboxylic acid ethyl ester (II) with N-(triphenylmethyl)-5-(4'-bromomethylbiphenyl-2-yl) tetrazole (III) in the presence of an organic solvent and an acid-binding agent. According to the preparation and purification method of the compound (I), the impurity content is effectively reduced, and the quality of a subsequent target productis improved. The method is stable in process, high in yield, good in quality, simple to operate, less in three wastes, low in production cost and suitable for industrial production, and the recoveredsolvent can be continuously used.

The invention provides a continuous hydrogenation method of ethyl pyrazine-2-carboxylate. The continuous hydrogenation method comprises the following steps: dispersing a mixture of ethyl pyrazine-2-carboxylate and hydrogen to form a gas-liquid mixture containing small liquid drops with sizes of 50 nm-5 mm, wherein the gas-liquid mixture is used as a reaction raw material; and continuously inputting the reaction raw material into a fixed bed reactor, carrying out a catalytic hydrogenation reaction, and continuously discharging ethyl pyrazine-2-carboxylate, wherein the fixed bed reactor is divided into at least two temperature control sections along the flowing direction of the material, and the temperature of the latter temperature control section is controlled to be lower than the temperature of the former temperature control section. According to the above forced dispersion process, the reaction raw material can be subjected to high-performance mass transfer in the catalytic hydrogenation reaction process, so the sufficient reaction degree of the reaction raw material is improved, and reaction time is shortened. The fixed bed reactor is subjected to sectional temperature controlalong the flowing direction of the material, so heat accumulation can be effectively removed, a reaction state in the reactor can be effectively controlled, and the yield, purity and product performance stability of a target product, namely ethyl pyrazine-2-carboxylate are improved.

The invention relates to a synthetic method of 6-chloroimidazo [1, 2-b]pyridazine-3-formic acid. The synthetic method comprises the steps of reacting N,N-dimethylformamide dimethyl acetal and 3-amino-6-chloropyridazine at the temperature of 40 to 120 DEG C to obtain an intermediate; under an alkali action, reacting at the temperature of 65 to 140 DEG C, and carrying out rotary evaporation and concentration to obtain a 6-chloroimidazo [1,2-b]pyridazine-3-formic acid ethyl ester crude product; recrystallizing the crude product to obtain a pure product; under an alkali action, carrying out hydrolysis reaction in a certain solvent, finishing reaction, neutralizing through hydrochloric acid, carrying out suction filtration, and washing drying to obtain a 6-chloroimidazo [1, 2-b]pyridazine-3-formic acid pure product. The synthetic method provided by the invention is adopted for preparing the 6-chloroimidazo [1, 2-b]pyridazine-3-formic acid, so that the reaction raw materials can be obtained easily, the method is easy to operate and control and simple in aftertreatment, and the product has stable quality and high purity.