33results about How to "Simple post-reaction handling" patented technology

The invention relates to a synthesis method of vilazodone and a salt thereof, belonging to the technical field of drug synthesis. The synthesis method comprises the following steps of: with 5-fluorin-2-hydroxybenzaldehyde as a raw material, subjecting the 5-fluorin-2-hydroxybenzaldehyde and acetobromamide to reaction under the action of an acid binding agent to obtain a compound as shown in the formula (I); subjecting piperazine and the compound (I) as shown in the formula (I) to reaction at the temperature of 100-140 DEG C under the action of alkaline to obtain a compound as shown in the formula (II); and subjecting 3-(4-chlorobutyl)-5-cyanoindole and the compound as shown in the formula (II) to reflux reaction for 14-18h under the actions of a catalyst and alkaline, and then, adding the product into an aqueous alkaline solution until a solid is separated out to obtain a compound as shown in the formula (III), namely the vilazodone, wherein the compounds as shown in the formulas (I), (II) and (III) respectively have the structural formulas in the specification. The synthesis method is low in production cost, environment-friendly, high in conversion ratio, few in byproducts, high in product yield and purity, good in quality and suitable for large-scale industrial production.

The invention discloses a chiral nitrogen oxygen bridge ring skeleton and spiro oxindole compound and a synthesis method of the compound. The method specifically comprises the following steps: takinga 3-pyrrolyl oxindole and beta,gamma-unsaturated alpha-keto ester derived from salicylaldehyde as a reactant, and in the presence of a chiral thiourea compound and bis(trifluoromethanesulfonyl)imide,performing an asymmetric tandem cyclization reaction in a methyl tert-butyl ether and toluene solvent to obtain a product. The method disclosed by the invention has simple and easily available raw materials, mild reaction conditions, simple and convenient post-treatment, wide application range, good yield, and high enantioselectivity and non-enantioselectivity; and therefore, the synthesized product has a potential medicinal value.

The invention provides a synthesis method of (R)-2-p-nitrobenzene ethylamine-1-phenethyl alcohol and salt thereof, belongs to the technical field of medicine synthesis and solves the problems that in the prior art the cost is high, the product yield is low, the synthesis method is not applicable to large-scale industrial production, and the like. The synthesis method comprises the following steps of: under the action of an oxidant, oxidizing hydroxyl on p-nitrobenzene ethanol into an aldehyde group so as to obtain p-nitrobenzene acetaldehyde; under the action of a reducing agent, carrying out dehydration, condensation and reduction on amino on (R)-2-amino-1-phenethyl alcohol and the aldehyde group on p-nitrobenzene acetaldehyde so as to obtain (R)-2-p-nitrobenzene ethylamine-1-phenethyl alcohol; and mixing a rough product of (R)-2-p-nitrobenzene ethylamine-1-phenethyl alcohol with an acid so as to generate precipitate or stirring till solid (R)-2-p-nitrobenzene ethylamine-1-phenethyl alcohol salt is separated out. The synthesis method of (R)-2-p-nitrobenzene ethylamine-1-phenethyl alcohol and the salt thereof is low cost and high in product yield, and is applicable to large-scale industrial production.

The invention discloses an energetic material 4, 4, 8, 8-tetranitroadamantane-2, 6-dinitrate and a preparation method thereof. According to the preparation method, cyclooctadiene as the raw material undergoes the steps of hydroboration-oxidation, oxidation, formylation, cyclization, nitric acid esterification, oximation, germinal nitration and the like to be finally synthesized into 4, 4, 8, 8-tetranitroadamantane-2, 6-dinitrate. Polynitroadamantane and adamantine nitrate have the advantages of symmetrical structure, high density, excellent explosion property, low sensitivity and the like, and can be widely used in the fields of explosives, propellants, pyrotechnic compositions, fuels and the like.

The invention relates to a preparation method and application of mannose-grafted trimethyl chitosan.The preparation method comprises: adding N,N,N-trimethyl chitosan into an organic solvent so that the organic solvent wells, adding mannopyran phenyl isothiocyanate for full reacting, and preparing N-mannose-N,N,N-trimethyl chitosan by ethanol washing, suction filtering and vacuum drying.The invention also provides application of the preparation method of the mannose-grafted trimethyl chitosan in the preparation of drug-carrying microspheres.The preparation method of a mannose-grafted trimethyl chitosan carrier has mild conditions, and a prepared mannose-grafted trimethyl chitosan drug-carrying microsphere preparation can target dendritic cells, overcoming mucosal barriers.

An oxo-bi(N-Methylphthalimide) synthesis method, which solves problems existing in prior art, such as long reaction time, incomplete reaction and low yield. The method comprises the following steps: adding N-methyl-4-nitrophthalimide, sodium carbonate, potash, N- methyl pyrrolidone, toluene and alkyl guanidine haloid into a three-neck flask; then heating for refluxing; cooling to room temperatureand pouring into water; filtering solid; washing and drying to finish. The method of the invention has moderate reaction conditions without requiring a waterless condition or an inert gas protection,a short reaction time, a complete reaction, and a simple post treatment. The product, which is easy to separate, has a yield higher than 85%, a melting point of 269-271 DEG C, and a high purity. In addition, the method with a reduced production costs is environment-friendly and suitable for large scale production.

The invention relates to the field of pharmacy and concretely relates to a novel synthesis route of alpha arylglycine. The preparation method comprises contracting an arylated metal complex through a transition metal-catalyzed coupling reaction of a halogenated aryl compound and a metal complex and carrying out arylated metal complex dissociation to realize alpha arylglycine preparation. The preparation method is simple and economic and is suitable for synthesis of alpha arylglycine with a novel structure type.

The invention relates to a synthesis method of a drug Tafamidis. According to the synthesis method, 3-hydroxy-4-amidobenzoic acid is used as a raw material, and the drug Tafamidis is prepared through esterification, amidation, cyclization and hydrolysis reaction. According to the method, concentrated sulfuric acid and methanol are used for replacing expensive and dangerous trimethylsilyl diazomethane to carry out methylation reaction of carboxyl; in the cyclization reaction, the dosage of p-toluenesulfonic acid is obviously reduced; reaction post-treatment is simplified, column chromatography for product purification is not needed in each step of reaction, the total yield of the reaction is remarkably increased, and the method is more suitable for industrial production.

The invention relates to a synthetic method of a peramivir intermediate, in particular to a synthetic method of a key intermediate by adopting an anti-influenza drug, namely peramivir, wherein the key intermediate is (3aR,4R,6S,6aS)-4-[[(1,1-dimethyl ethoxy) carbonyl] amino]-3-(1'-ethyl propyl)-3a,5,6,6a-tetralin-tetrahydro-4H-cyclopentano[d]isoxazole-6-carboxylic acid ammonium tertiary butyl (compound IV). According to the synthetic method of peramivir intermediate, provided by the invention, (1S,4R)-(-)-[[(1,1-dimethyl ethoxy)carbonyl]amino]cyclopentyl-2-alkenyl-1- carboxylic acid methyl ester (compound I) is taken as the raw material (preparation reference patent is CN101367750B) to be subjected to ring-closure reaction with butyric imine acyl chloride under catalyzation of a metal catalyst, so that the target compound is formed. According to the synthetic method of peramivir intermediate, provided by the invention, the low-cost, easily available and efficient metal catalyst is used, in addition, compared with the conventional technological process, the synthetic method is obviously increased in the yield, the technological process is simple, and industrial large-scale production is facilitated.

The invention discloses a preparation method of di-tert-butyl iminodiacetate. The method is characterized in that ammonia and tert-butyl chloroacetate are used as raw materials. The method comprises the following steps: carrying out a reaction between ammonia and tert-butyl chloroacetate based on the molar ratio of 1:(1-6) in an organic solvent under a closed condition, wherein the reaction temperature is 10-65 DEG C, the reaction pressure is normal pressure, and the reaction lasts for 2-10h; after the reaction ends, cooling until the room temperature is reached; filtering; rotatably evaporating the filtrate to remove the organic solvent; then cooling to reach the temperature of 0 DEG C to obtain a solid which is di-tert-butyl iminodiacetate. According to the method, the solvent is nontoxic and free of pollution; the solvent is recycled; no catalyst or cocatalyst is used; the reaction separation method is simple; the di-tert-butyl iminodiacetate yield is high.

The invention discloses a continuous synthesis process and device of 3bromopyridine, which comprises the following steps: respectively pumping pyridine, hydrobromic acid and hydrogen peroxide into a mixer according to a certain proportion, mixing by the mixer, and reacting in a first-stage tubular reactor and a second-stage tubular reactor; a reaction solution obtained after the reaction of the first-section tubular reactor and the second-section tubular reactor enters a first condenser to be cooled, the cooled reaction solution enters a continuous neutralization and liquid separation device,and meanwhile a sodium hydroxide solution is added into the continuous neutralization and liquid separation device; an upper-layer water phase of the continuous neutralization liquid separation deviceenters a wastewater storage tank, a lower-layer organic phase is evaporated and flashed by a negative-pressure film evaporator to remove low-boiling-point substances brought by separated liquid and then enters a negative-pressure rectifying tower to be rectified, the reflux ratio is controlled, a product at the top of the negative-pressure rectifying tower is collected by a product storage tank,and a bottom material at the bottom of the negative-pressure rectifying tower can be used as high-calorific-value fuel. The method can effectively solve the problems in 3bromopyridine synthesis, improves the production efficiency, reduces the energy consumption, and saves the production cost.

The invention discloses a preparation method for a cyan coupler intermediate. The preparation method comprises the following steps: with 4-t-butyl-benzoylhydrazine and ethyl 3-ethoxy-3-iminopropionate as raw materials, reacting 4-t-butyl-benzoylhydrazine with ethyl 3-ethoxy-3-iminopropionate in a lower-ester solvent at 50 to 100 DEG C, carrying out cooling to room temperature after completion of the reaction and then carrying out filtering so as to obtain ethyl 3-[2-(4-t-butyl-phenyl)-hydrazyl]-3-iminopropionate used as a transition intermediate; and subjecting ethyl 3-[2-(4-t-butyl-phenyl)-hydrazyl]-3-iminopropionate to reaction in an alkaline aqueous solution at 70 to 90 DEG C, carrying out cooling to room temperature after completion of the reaction, and successively carrying out neutralization via halogenated acid, filtering and drying so as to obtain the cyan coupler intermediate 2-[3-(4-t-butyl-phenyl)-1H-1,2,4-triazolyl-5]-propionic acid.