111 results about "Lithium diisopropylamide" patented technology

A parecoxib preparation method comprises the following steps: reacting diacetophenone oxime with ethyl acetate in a lithium diisopropylamide/tetrahydrofuran system to generate 4,5-dihydro-5-methyl-5-hydroxy-3,4-dibenzylisoxzzole; reacting 4,5-dihydro-5-methyl-5-hydroxy-3,4-dibenzylisoxzzole with halogenated sulfonic acid, and ammonolyzing to obtain valdecoxib; and reacting valdecoxib with propionic anhydride to obtain parecoxib. Compared with the prior art, the preparation method disclosed in the invention has the advantages of low initial raw material cost, simple and feasible technological process, low equipment requirement, and suitableness for the industrialized large-scale production.

The invention discloses a compounding method for 3- ethyoxyl-4-ethoxycarbonyl phenylacetic acid, comprising the following steps: making 4-methyl salicylate and bromoethane which are used as starting raw materials to carry out double alkylation reaction in N,N-dimethylformamide to prepare 2-ethyoxyl-4-ethyl methylbenzoate; directly dissolving the unpurified 2-ethyoxyl-4-ethyl methylbenzoate into 2-methyl tetrahydrofuran, adding lithium diisopropylamide, and introducing carbon dioxide; acidizing the mixture by sulphuric acid to prepare the 3-ethyoxyl-4-ethoxycarbonyl phenylacetic acid. The product of the invention is white powders with a melting point of 78 to 80 degrees and the content of 99.4%. In the invention, the solvent of N, N-dimethylformamide and 2-methyl tetrahydrofuran can be recycled and repeatedly applied. The invention has the advantages of simple operation, environment friendliness, simple industrial operation, industrial production realization and low cost due to the adoption of the common industrial raw materials.

The invention relates to the application of lithium diisopropylamide which is an organic alkali in preparing 1-methylcyclopropene; the application of the lithium diisopropylamide as a catalyst to prepare the 1-methylcyclopropene well solves the technical problem that the production course of the 1-methylcyclopropene has high energy consumption, low content and high cost, simplifies the production processes, reduces the production costs and realizes high yield of 1-methylcyclopropene.

The invention discloses a beta-hydroxy imine titanium metal catalyst for polymerizing ethylene and a method for polymerizing ethylene. The catalyst can be prepared by the following steps: reacting an imide compound with lithium diisopropylamide; reacting the reacted imide compound with aldehyde or ketone to generate a beta-hydroxy imine ligand; and reacting the ligand with a titanium metal compound to generate the beta-hydroxy imine titanium metal catalyst. By adjusting the substituent group structure of the imide compound and the types of the aldehyde or ketone and the polymerization conditions, the controllability of the catalytic polymerization on the ethylene can be realized. The catalyst is a novel non-metallocene transition metal catalyst and has the characteristics of novel structure, high catalytic activity, easily-accessible raw materials, convenient preparation and the like.

The invention provides a preparation method for obeticholic acid. The preparation method comprises the following steps of: adding 3alpha-hydroxyl-7-keto-5beta-cholanic acid and methanol into a reaction container and carrying out esterification reaction in an acidic environment to obtain 3alpha-hydroxyl-7-keto-5beta-methyl cholanate; adding 3,4-dihydro-2H-pyran and dioxane and protecting hydroxyl by tetrahydropyrane ether; adding bromoethane, lithium diisopropylamide and site alpha of diastereomeric methylated keto-carbonyl; then adding methanol, removing the protecting group which protects tetrahydropyrane ether and reducing hydroxyl in the acidic environment; adding sodium borohydride and reducing the mixture to 3alpha-hydroxyl-6beta-methyl-7-hydroxyl-5beta-methyl cholanate; and adding methanol and carrying out alkali hydrolysis to obtain 3alpha-hydroxyl-6beta-methyl-7-hydroxyl-5beta-cholanic acid, namely the target product obeticholic acid. According to the preparation method provided by the invention, the process line is mild in reaction, simple to operate and high in yield.

The invention provides a seedling culture method for interplanting of paeonia suffruticosa for oil and garlic and relates to the technical field of paeonia suffruticosa planting. The method comprises the steps of sowing seeds of paeonia suffruticosa for oil and garlic at the same time from the beginning of September to the beginning of October; selecting seeds by using a water selection method before sowing, soaking the seeds in a mixed liquid of potassium pyrophosphate and lithium diisopropylamide with a mass concentration of 1-5% and at a temperature of 40-50 DEG C for 20-40 hours, the mass ratio of the potassium pyrophosphate to the lithium diisopropylamide being 3-4:1, and performing disinfection treatment on the seeds for sowing when the seeds fully absorb water and expand; during seeding, maintaining a field moisture capacity of 65-75%, forming furrows 8-12cm deep and 4-5cm wide with a line spacing of 15-20cm in ready-made high ridges for sowing seeds, scattering the seeds in the furrows uniformly with a distance of 1-2cm, and covering the seeds with 3-5cm soil; performing field management. The method has the advantages of good germination accelerating effect, high germination rate, high survival rate, simple and convenient operation and low cost.

The invention discloses an obeticholic acid preparation method, which comprises that (1) hyodeoxycholic acid II reacts with an alcohol compound III under the action of a catalyst to generate an ester compound IV; (2) the ester compound IV is subjected to PDC oxidation in dichloromethane to generate a compound V; (3) the compound V and trimethyl chlorosilane are subjected to a reaction at a temperature of -70 to -20 DEG C in tetrahydrofuran by using lithium diisopropylamide as an alkali to generate a silyl enol ether compound VI; (4) the silyl enol ether compound VI is subjected to m-chloroperoxybenzoic acid oxidation and deprotection in dichloromethane to generate a compound VII: (5) the compound VII and Yield generated from ethyltriphenylphosphonium bromide under the action of a strong alkali are subjected to a Wittig alkenylation reaction at a temperature of 0-70 DEG C to convert the ketone into the vinyl so as to generate a compound VIII; (6) the double bond of the compound VIII is subjected to catalytic hydrogenation reduction in a mixing solvent to generate a compound IX; and (7) the compound IX is hydrolyzed under an alkaline condition to generate the obeticholic acid.

The invention relates to a ratio two-photon and near-infrared HClO detection fluorescence probe as well as preparation and application thereof and belongs to the technical fields of synthesis and detection. The structural formula of the fluorescence probe is as shown in the specification. The fluorescence probe is prepared by the following steps: 1, reacting 4-(diethylamino) salicylaldehyde with ethyl acetoacetate and piperidine; 2, enabling 4-diethylaminobenzaldehyde to participate in the reaction; and 3, enabling cyclohexene to participate in the reaction to obtain a compound, respectively reacting the compound with lithium diisopropylamide and phenylselenenyl bromide, thereby obtaining the fluorescence probe. The probe can be reacted with the HClO to produce olefinic bonds, wavelength red shift is caused by the enlarged conjugated structure, and the ratio fluorescence change of which the short wavelength fluorescence intensity is reduced and long wavelength fluorescence intensity isenhanced is formed. Therefore, the design of the probe based on the Sharpless alkene synthesis reaction can be used for detecting the HClO, and the probe is simple in structure and has the advantagesof being high in selectivity, high in sensitivity, fast in transient response and the like.

The invention discloses a preparation process of aprepitant. The process comprises the steps as follows: Step 1, a compound A and a compound B are firstly added to a mixed solvent of N,N-dimethylformamide and triethylamine to be stirred and dissolved to obtain a mixed solution; Step2, adding lithium diisopropylamide to the mixed solution in a nitrogen atmosphere and performing uniform mixing; Step3, dropwise adding a diethyl sulfate xylene solution under conditions of nitrogen shielding and stirring; Step 4, after addition, conducting a stirring reaction at 30-35 DEG C for 12-15 h under shielding of nitrogen; Step 5, separating and purifying a reaction product in Step 4 to obtain a final aprepitant product. By process improvement and formula optimization, the aprepitant synthesis processhas the characteristics of mild reaction condition, low cost and the like and is suitable for large-scale industrial production; the synthesized aprepitant product has low impurity content and high purity, and the yield of aprepitant is greatly increased.

The invention relates to the technical field of medical intermediates, in particular to a synthetic method of a remdesivir intermediate. The chemical name of the intermediate is (3R,4R,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-di(benzyloxy)-5-((benzyloxy)methyl)tetrahydrofuran-2-ol. The preparation method comprises the following steps: performing amino protection on pyrrolo[2,1-F][1,2,4]triazin-4-amine with a protecting agent; reacting with lithium diisopropylamide; then adding 2,3,5-tribenzyloxy-D-ribonic acid 1,4-lactone, and finally removing the protective group to obtain the remdesivir intermediate that is the (3R,4R,5R)-2-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-di(benzyloxy)-5-((benzyloxy)methyl)tetrahydrofuran-2-ol.

The invention relates to a preparation method of voriconazole, wherein the preparation method comprises the following specific steps: adding alpha-fluoropropionyl ethyl acetate and a methanol solution of formamidine acetate into a methanol solution of sodium methylate, carrying out cyclization to obtain 6-ethyl-5-fluoropyrimidine-4(3H)-one, chloridizing to obtain 4-chloro-6-ethyl-5-fluoropyrimidine, dissolving 4-chloro-6-ethyl-5-fluoropyrimidine in tetrahydrofuran, dropwise adding into a tetrahydrofuran solution of lithium diisopropylamide, adding a tetrahydrofuran solution of 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazole-1-yl)ethyl ketone, carrying out a reaction to obtain 3-(4-chloro-5-fluoropyrimidine-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazole-1-yl)butyl-2-ol, dissolving in ethanol, adding 10% palladium-carbon and sodium acetate, and then splitting to obtain voriconazole. According to the preparation method of voriconazole, the preparation method is simple, and the production cost is low.

The invention provides a new method for synthesizing sophocarpine. The method comprises the following steps: removing alpha-position hydrogen in amide in matrine by taking matrine as a raw material and taking lithium diisopropylamide (LDA) as alkali, then directly performing nucleophilic substitution reaction with diphenyl disulfide to obtain 14-thiophenyl matrine, oxidizing by IBX (o-iodyl-benzoic acid) in a water phase to obtain 14-phenylsulfinyl matrine and eliminating benzenesulfenic acid under the assistance of weak alkali to obtain sophocarpine. The method provided by the invention takes the step of oxidizing a nitrogen-containing thioether compound with IBX in a water phase to form sulfoxide as the key step for synthesizing sophocarpine. The method is characterized by high efficiency, environmental friendliness and easiness in operation. The synthesis route is as shown in the description.

The invention discloses a synthesis method of 3-bromine-2-fluorobenzoic acid, and belongs to the field of organic synthesis. The synthesis method of the 3-bromine-2-fluorobenzoic acid comprises the following steps: taking fluorobenzene as a starting material, deprotonating lithium diisopropylamide, carrying out a reaction with trimethylchlorosilane to generate 2-fluorophenyl trimethylsilane, forming an intermediate 3-trimethyl silicon-2-fluorinated phenyl lithium salt, carrying out a reaction with carbon dioxide to generate 3-trimethyl silicon-2-fluorobenzoic acid, and carrying out a reactionwith a bromide reagent to obtain the 3-bromine-2-fluorobenzoic acid. The intermediate obtained by the method avoids separation of an isomer, the obtained product has high purity, and a concise approach is provided for synthesis of the compound.

The invention discloses an amino acid compound containing a diaziridine group and a synthesis method thereof. The method comprises the following steps: with ethyl acetoacetate as a raw material, performing a reaction under the action of lithium diisopropylamide; performing a reaction with propargyl bromide to generate 3-oxoheptyl-6-acetylenic acid ethyl ester; then hydrolyzing the reaction productto generate 3-oxoheptyl-6-acetylenic acid, so as to obtain 3-oxoheptyl-6-acetylenic acid; then performing a reaction with hydroxylamine-O-sulfonic acid in an ammonia gas methanol solution; performingiodine elementary substance oxidation to generate 2-(3-(butyl-3-acetylene-1-yl)-3H-diaziridine-3-yl)acetic acid; then carrying out a reaction on 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide to generate 2,5-dioxopyrrolidine-1-yl-2-(3-(butyl-3-yl-1-yl)-3H-diaziridine-3-yl)acetate, and then carrying out a reaction with amino acid molecules to generate the targetproducts. The compound synthesized by the invention contains diaziridine groups and amino acid molecules with biological activity, and can be used in biological activity test and analysis.

The invention provides a temperature-control seedling raising method of rice in a greenhouse, and relates to the technical field of planting of rice. The method comprises the following steps of building the greenhouse; performing sowing in good time; treating seeds: firstly, selecting seeds by a water test method before sowing, soaking the seeds with mixed liquid of potassium pyrophosphate and lithium diisopropylamide, of which the mass concentration is 1-5% at 15-20 DEG C, for 2-3 days, wherein the proportion of the potassium pyrophosphate to the ithium diisopropylamide being (3-4) to 1, finding that rice husk is translucent, the rice bodies are white and clear, and the germs are expanded through observation, and performing disinfection treatment; then performing coating with a coating material, performing drying until sticking hands disappears, and then performing sowing; performing a sowing method; and performing field management. The germination accelerating effect is good, the germination percentage is high, the survival rate is high, the operation is simple and convenient and the cost is low.

The invention discloses a seedling growing method for oil peonies, and relates to the technical field of peony planting. The seedling growing method is characterized by including the following steps that the seeding time of oil peonies is selected to be from early September to early October; before seeding, seed selection is carried out with the water selecting method, seed soaking is carried out for 20 hours to 40 hours with mixed liquid of potassium pyrophosphate with the mass concentration of 1%-5% at the temperature of 40 DEG C to 50 DEG C and lithium diisopropylamide, the mass ratio of the potassium pyrophosphate to the lithium diisopropylamide is (3-4):1, and after seeds fully absorb water, swell and are disinfected, seeds can be used for seeding; seeding is carried out with the seeding method, the field water capacity is 65% to 75%, ditching and seeding are carried out on made high ridges, ditching is carried out according to the row spacing of 15 cm to 20 cm, the ditch depth is 8 cm to 12 cm, the width is 4 cm to 5 cm, seeds are evenly scattered into ditches, the intervals between seeds is 1 cm to 2 cm, and then 3-5-cm earthing is carried out; field management is carried out. The seedling growing method is good in sprouting effect, high in germination rate and survival rate, easy and convenient to operate and low in cost.

The invention belongs to the field of medicine synthesis, and relates to a novel synthesis method of a compound bepidic acid. The preparation method comprises the following steps: (1) carrying out primary alkylation on ethyl isobutyrate and 1, 5-dibromopentane under the action of lithium diisopropylamide to generate a compound 1; (2) carrying out alkylation twice on dibenzyl malonate and the compound 1 under the action of sodium hydride to generate a compound 2; (3) removing benzyl from the compound 2 under the action of Pd/C and hydrogen to obtain a compound 3; (4) carrying out electrochemical reaction on the compound 3 in a methanol solution of methanol and ammonia to obtain a compound 4; (5) finally carrying out sodium borohydride hydrolysis and potassium hydroxide hydrolysis on the compound 4, and acidifying to obtain the final bepidic acid. The method is carried out under electrochemical conditions, is mild in conditions and high in efficiency, and is suitable for industrial production.

A method of preparing 2,4,6-trifluorobenzaldehyde is provided. The method includes (1) preparing a tetrahydrofuran solution of lithium diisopropylamide, and keeping the solution for later use; (2) cooling to a temperature ranging from -85 DEG C to -80 DEG C, adding dropwise the tetrahydrofuran solution of the lithium diisopropylamide into a tetrahydrofuran solution of 1,3,5-trifluorobenzene under nitrogen protection, and reacting at a maintained temperature for 3-5 h after the addition is finished; (3) adding dropwise dimethylformamide into the reaction solution, and maintaining the temperature at a temperature ranging from -80 DEG C to -75 DEG C for 50-70 min; (4) maintaining the temperature to be -5-0 DEG C, adding dropwise glacial acetic acid, water and diluted hydrochloric acid in order into the reaction solution, adjusting the pH to be 1-2, and stirring the solution for 10-20 min after addition is finished to obtain a crude product; and (5) subjecting the crude product to after-treatment to obtain a target product that is the 2,4,6-trifluorobenzaldehyde. The lithium diisopropylamide that is a non-nucleophilic organic base is applied, thus providing a novel route for preparing the 2,4,6-trifluorobenzaldehyde.

The invention discloses a novel preparation method for a butyrolactone derivative. The method includes the steps of: (1) reacting pentanoic acid shown as formula (II) with ethyl bromoacetate under theaction of lithium diisopropylamide to obtain a compound shown as formula (III); (2) splitting the compound shown as formula (III) with chiral phenylethylamine to obtain a compound shown as formula (IV); (3) subjecting the compound shown as formula (IV) to reduction of carboxyl by borane so as to obtain a compound shown as formula (V); and (4) carrying out cyclization reaction on the compound shown as formula (V) to obtain a butyrolactone derivative shown as formula (I). The brand new butyrolactone derivative synthesis method provided by the invention has the advantages of low cost of synthetic raw material pentanoic acid, need of just 4-step reaction, and good stereoselectivity, and can obviously reduce the production cost. And the synthesis route is shown as the specification.

The invention relates to a thiophene macrocyclic compound and a preparation method of derivatives of the thiophene macrocyclic compound, in particular to a preparation method of a thiophene eight membered cyclic compound and a thiophene twelve membered cyclic compound. The preparation method is as follows: 2, 2`-dibromo-[3, 3`]-bithiophene is adopted as the raw material; lithium diisopropylamide (LDA) is firstly used to capture the Alpha- proton, then the 2, 2`-dibromo-[3, 3`]-bithiophene is quenched by trimethylchlorosilane, and a compound 3 is prepared; then the compound 3 and butyl lithium generate bromine and lithium exchanging reaction, and copper chloride oxidative cyclization is used to generate thiophene eight membered cyclic compound 4 and thiophene twelve membered cyclic compound 5, wherein, the yield of the compound 5 reaches up to 36 percent; and in the condition that trifluoroacetic exists, the compound 4 and the compound 5 remove TMS, and a compound 1-four (2,3-bithiophene) and a compound 2-six (2,3-bithiophene) are obtained. The preparation method of the derivatives of the thiophene macrocyclic compound realizes the aim of preparing the thiophene eight-membered cyclic compound at high yield, and most importantly, the preparation method realizes the aim of preparing the thiophene twelve-membered cyclic compound at high yield, and the total yield of the three steps reaches up to 27 percent. The synthetic process of the method has operability, and the reaction conditions of waterless, oxygen free and low-temperatured. Thus, the preparation method is suitable for scale preparation.