39results about How to "Improve the overall yield of synthesis" patented technology

The invention discloses a preparation method of nomegestrol acetate. The method comprises that gestonorone acetate as a raw material is dissolved in an organic solvent and then undergoes a reaction with ethylene glycol under acid catalysis in the presence of triethyl orthoformate to produce diketal, the diketal is dissolved in an organic solvent and undergoes a reaction with hydrogen peroxide under alkali catalysis to produce an epoxy compound, the epoxy compound is dissolved in an organic solvent and undergoes a Grignard addition reaction with methylmagnesium halide, the reaction product is hydrolyzed in a strong acid solution and is subjected to dehydration deprotection so that a methyl compound is obtained, and the methyl compound is dissolved in an organic solvent and undergoes a dehydrogenation reaction with tetrachloro-p-benzoquinone to produce nomegestrol acetate. The nomegestrol acetate has HPLC content of 99.0-99. 5% and a four-step synthesis total yield of 60-62%. Compared with the traditional method, the method has the advantages of simple and convenient operation, economy, environmental friendliness, high total synthesis yield and good product quality and reduces a costby 35-40%. The solvent used by the method can be recovered and recycled and is conducive to industrial production.

The invention provides a method for preparing a compound containing isochroman-1-one skeleton, specifically methyl o-iodobenzoate substituted with substituents and 1, The 1-disubstituted olefin is used as a raw material, and a compound containing an isochroman-1-one skeleton is prepared through a cross-coupling reaction. The method does not use any directing group, and no additional steps are required to introduce or remove the directing group; the method has a wide range of functional groups and the tolerance of the functional group; the method has the advantages of cheap and easy-to-obtain raw materials, simple steps, and high overall yield of synthesis , The advantages of low total cost of synthesis. The prepared isochroman-1-one skeleton-containing compound has broad application prospects in the synthesis of pesticides, pharmaceutical intermediates, complex natural products, and the like.

The invention relates to the technical field of a preparation method of thiophene derivatives, in particular to a preparation method of 3-(thiophene-2-yl)hexanaphthene-2-ketene derivatives. The preparation method of the 3-(thiophene-2-yl)hexanaphthene-2-ketene derivatives comprises the following steps: (1) adding cyclohexenone, thiophene or substituted thiophene, palladium chloride, silver carbonate, N-acetoglycocoll and silver hexafluoroantimonate into a reactor sequentially according to the molar ratio of 3:1:0.1:2.5:0.1:0.2, adding a solvent to dissolve the reactants, mixing uniformly at a room temperature, and reacting at 60 to 120 DEG C for 5 to 48 hours; (2) after the reaction, cooling the reactor to a room temperature, dissolving with ethyl acetate, washing with a saturated ammonium chloride aqueous solution and a saturated sodium chloride aqueous solution sequentially, drying the organic phase by using anhydrous sodium sulfate, filtering and rotating on a rotary evaporator to remove the solvent; (3) separating and purifying the residues through silica-gel column chromatography after the solvent is removed through rotation, collecting a target product, performing rotary evaporation to remove the solvent, and pumping and drying by an oil pump.

The invention provides a new method for preparing 16alpha-hydroxyprednisolone. The method comprises the following steps that A, a protector is prepared, wherein prednisolone acetate and trimethylchlorosilane are catalyzed by organic base to generate a 11th-site silicon etherification reaction, and then the protector is obtained; B, dehydration, hydrolysis deprotection and refining are conducted, wherein the protector and SO3 are catalyzed by organic base to generate a 17th-site dehydration reaction, after the reaction, acid is directly added to make the 11th site deprotected, and a crude 17alpha-dehydroxylated prednisolone acetate product is obtained; the crude product is refined to obtain a 17alpha-dehydroxylated prednisolone acetate product; C, the 17alpha-dehydroxylated prednisolone acetate product is used as a raw material to prepare the 16alpha-hydroxyprednisolone. The problems are solved that in a traditional production technology of the 17alpha-dehydroxylated prednisolone acetate, more side reactions and impurities are generated in the dehydration process, and the impurities are difficult to refine; the total yield of the synthesized 16alpha-hydroxyprednisolone is greatly improved, and the production cost is reduced.

The invention discloses a method for preparing 16a-hydroxy prednisolone. The method includes the steps of adopting 17a-dehydroxyl prednisolone as a raw material and making the 16th locus and 17th locus of initial raw material 17a-dehydroxyl prednisolone subjected to an epoxidation reaction with organic peracid in a first organic solvent to obtain an epoxy object; making the epoxy object reacted with glacial acetic acid for ring opening under catalysis of acid catalysts in a second organic solvent to obtain 16a,21-diacetoxy prednisolone; then dissolving 16a,21-diacetoxy prednisolone in a thirdorganic solvent, hydrolyzing acetate at two positions under the catalytic action of a solid-phase base catalyst, and preparing 16a-hydroxy prednisolone, wherein the solid-phase base catalyst adopts aluminum oxide and silica gel or calcium carbonate as carriers, and the catalysts of sodium carbonate or sodium hydroxide are adsorbed on the carriers. 16a-hydroxy prednisolone is prepared by means of the efficient, environment-friendly and economical method.

The invention provides a method for preparing a 16a-hydroxyprednisolone product. The method comprises the steps that 17a-dehydroprednisolone is used as a raw material, and firstly the starting material 17a-dehydroprednisolone performs an epoxidation reaction with organic peroxide acid at 16 and 17 sites in a first organic solvent to prepare an epoxy material; then the epoxy material reacts with glacial acetic acid under catalysis of an acid catalyst in a second solvent for loop opening, and thus 16a,21-diacetoxyprednisolone is prepared; 16a,21-diacetoxyprednisolone is dissolved in a third organic solvent, under the catalytic action of a solid-phase base catalyst, acetic ester on the two sites are hydrolyzed, and thus 16a-hydroxyprednisolone is prepared; and finally the 16a-hydroxyprednisolone crude product obtained by solid-phase base-catalyzed hydrolysis is heated and refluxed, decolorized, and recrystallized through low-carbon alcohol below C4, and thus the 16a-hydroxyprednisolone product is obtained. According to the method, 16a-hydroxyprednisolone is prepared in an efficient, environment-friendly and low-cost mode.

The invention provides a preparation method of a 17a-dehydroxy prednisolone acetate product. The method includes the following steps: step A, dissolving prednisolone acetate in a first organic solvent, and subjecting the solvent and trimethylchlorosilane to 11th-position silicon etherification reaction under the catalysis of organic base to obtain a protector; step B, in a second organic solvent,subjecting the protector and SO3 to 17th-position dehydration reaction under the catalysis of the organic base, directly adding acid for treatment after the reaction to deprotect the 11th position, and obtaining a crude 17a-dehydroxy prednisolone acetate product; subjecting the crude product to decolorization and recrystallization in the presence of C4-below low carbon alcohol and activated carbonto obtain the 17a-dehydroxy prednisolone acetate product. The preparation method has the advantages that the problems such as many side reactions and impurities and difficulty in impurity refining inthe dehydration reaction in a traditional production process of 17a-dehydroxy prednisolone acetate are solved, the total synthesis yield is remarkably increased, and the production cost is reduced.

The invention provides a method for preparing 16a,21-diacetyloxy prednisolone. The method comprises the following steps: adopting 17a-deshydroxy prednisolone as a raw material, firstly, enabling the starting raw material 17a-deshydroxy prednisolone to generate epoxidation reaction with organic peroxy acid on 16 and 17 sites in a first organic solvent to prepare an epoxy product; enabling the epoxyproduct to react with glacial acetic acid under the catalysis of an acid catalyst in a second organic solvent to be subjected to ring opening, to prepare a target product, i.e., 16a,21-diacetyloxy prednisolone. According to the efficient, environment-friendly and fair-price method, the intermediate 16a,21-diacetyloxy prednisolone of 16 alpha-hydroxyprednisolone is prepared.

The invention discloses a preparation method of 16a-hydroxy prednisolone. The preparation method comprises the following steps: dissolving 16a-hydroxy prednisolone acetate into an organic solvent, adding an inert solid carrier adsorbed with strong base as a hydrolysis reaction solid-phase base catalyst, and hydrolyzing 21-acetate to obtain a 16a-hydroxy prednisolone crude product; and carrying out lower alcohol recrystallization on the crude product under the condition of below C4 to obtain a 16a-hydroxy prednisolone competitive product, wherein the refined weight yield is 85% to 90%, and the preparation weight total yield is 75% to 80%. The solid carrier is selected from aluminum oxide, silica gel or calcium carbonate; the base catalyst is selected from sodium carbonate; and the organic solvent is selected from methylbenzene or chloroform. Compared with a traditional method, the method disclosed by the invention is simple and convenient in production operation, impurities generated in traditional production can be greatly reduced, and the total yield for synthesis is greatly improved; compared with the traditional method, the production cost is reduced by 10% to 15%; and a synthetic reaction solvent can be recycled, and industrial production is facilitated.

The invention provides a preparation method of finished 16alpha,21-diacetoxy prednisolone product, comprising: subjecting 17alpha-deshydroxy prednisolone acetate as an initial material to 16,17-epoxidation with an organic peroxy acid in a first organic solvent to obtain an epoxide; subjecting the epoxide, in a second organic solvent, to ring-opening reaction with glacial acetic acid under the catalysis of an acid catalyst to obtain the target product, 16alpha,21-diacetoxy prednisolone; subjecting the crude 16alpha,21-diacetoxy prednisolone to heating reflux discoloration and crystallization with a lower carbon alcohol of C4 and below so as to obtain the finished 16alpha,21-diacetoxy prednisolone. The intermediate, 16alpha,21-diacetoxy prednisolone, to 16alpha-hydroxy prednisolone is prepared herein via the method that is efficient, environmentally friendly and fair in cost.

The invention provides a megestrol acetate preparation method. The method comprises the steps that 6-keto-17a-acetoxy progesterone serves as the raw material, the raw material is dissolved into an organic solvent, in the presence of triethyl orthoformate, a catalytic reaction is conducted with glycolic acid, and double ketals are obtained; the double ketals are dissolved into an organic solvent, a Grignard reaction is conducted with a Grignard reagent, after the reaction is completed, under the strong acid effect, Grignard hydrolysis is conducted, deprotection and dehydration are conducted simultaneously, and a crude megestrol acetate product is synthesized through a two-step reaction; the crude product is subjected to decoloration and recrystallization through activated carbon, and a megestrol acetate product is obtained, wherein the HPLC content ranges from 99.0% to 99.5%, the melting point ranges from 213 DEG C to 220 DEG C, and the two-step synthetic weight total yield ranges from 80% to 85%. Accordingly, compared with a traditional method, the synthetic route is short, the technological operation is easy and convenient, production is economical and environmentally friendly, the synthetic total yield is increased by 30% or above compared with that of the traditional method, and the production cost is lowered by 30%-35%; the solvents used in the technology can be recycled and applied mechanically, economy and environmental friendliness are achieved, and the method is very beneficial to industrial production.

The invention belongs to the technical field of preparation methods of indolated cyclohexenone derivatives, and specifically relates to a preparation method of 3-position indolated cyclohexenone compounds. The steps are as follows: molar ratio 1:4:0.1:0.2 :1.5 Indole or substituted indole, cyclohexenone, palladium trifluoroacetate, 2,5-dimethyl-8-trifluoromethyl-3,4-dihydro-2H-pyrano[2 ,3‑b] Add quinoline and tert-butanol peroxide into the reactor, add solvent to dissolve and mix well, react at 50°C for 24 to 41 hours; after the reaction is completed, cool to room temperature, dilute the reactant and wash with saturated aqueous sodium chloride solution , separating the organic phase from the aqueous phase, extracting the aqueous layer with ethyl acetate, combining the organic phases, filtering, and spinning off the solvent; separating and purifying the residue after spinning off the solvent, spinning off the solvent, and pumping dry to obtain the target product. The preparation method has the advantages of cheap and easy-to-obtain raw materials, simple reaction steps, high atom utilization rate and the like.

The invention discloses a method for extracting a nitration product from N-ethyl carbazole nitration solvent distillation residue. The method is characterized by comprising the following steps of: putting the N-ethyl carbazole nitration solvent distillation residue and an organic solvent in a container, heating while stirring to a reflux state, stirring for 0.5-6 hours while preserving heat, adding a flocculant and continuing stirring for 0.5-6 hours while preserving heat, and then filtering while the solution is hot or taking out the supernatant liquid from the container after standing, thereby obtaining 3-nitro-N-ethyl carbazole solution; and in order to improve the quality of the 3-nitro-N-ethyl carbazole solution, further adding active carbon to the solution for absorption bleaching, and after stirring for 0.5-6 hours while preserving heat, filtering while the solution is hot, thereby obtaining the solution of 3-nitro-N-ethyl carbazole. The method for extracting the nitration product from N-ethyl carbazole nitration solvent distillation residue has the advantages that the extraction process is simple and high in efficiency, the yield of permanent violet nitration is greatly improved and further the total yield of permanent violet synthesis is improved, the production cost of permanent violet is reduced, the waste residue is reduced and the environmental protection effect is good.