34 results about "Butoconazole Nitrate" patented technology

The invention relates to a medicinal composition for vagina. The composition comprises butoconazole nitrate, poloxamer, hydroxypropyl methylcellulose, Carbomer and other additives. The composition has the characteristics of good vagina mucosa adhesion and long-acting slow release, and in vivo and in vitro experiment results prove that the composition can continuously release the medicament for more than 72 hours.

The invention relates to a method for industrially producing a butoconazole nitrate intermediate 1-(2-chloro-4-(4-chlorphenyl)butyl)-1-hydro-imidazole. The method comprises the following steps: (1) taking 1-(2-hydroxy-4-(4-chlorphenyl)butyl)-1-hydro-imidazole and thionyl chloride as raw materials to undergo heating reflux in dichloromethane, and after full reaction, cooling the reactant, thus obtaining a reaction liquid; and (2) slowly adding cold water and anhydrous sodium carbonate to the reaction liquid obtained in the step (1) in sequence, carrying out suction filtration, discarding the solid, concentrating the liquid and drying the concentrate, thus obtaining the butoconazole nitrate intermediate. In the method provided by the invention, the conditions and parameters in the synthetic process are comprehensively and preferentially selected, thus increasing the purity and yield of the product. Therefore, the method is more suitable for large-scale industrial production.

The invention relates to a method for industrially producing butoconazole nitrate. The method comprises the following steps: (1) taking 1-8 parts of 1-(2-chloro-4-(4-chlorphenyl)butyl)-1-hydro-imidazole, 1-8 parts of 2,6-dichlorothiophenol, 1-5 parts of anhydrous potassium carbonate and 30-50 parts of acetone to undergo heating reflux reaction for 4-6 hours, then replenishing 0.1-1 part of anhydrous potassium carbonate, continuously carrying out heating reflux reaction for 5-9 hours, cooling and filtering the reactant and concentrating the filtrate, thus obtaining a concentrate; (2) taking the concentrate obtained in the step (1), adding extract liquor formed by an organic solvent and water, and after full extraction, retaining an organic phase for later use; (3) dropwise adding concentrated nitric acid to the organic phase obtained in the step (2) and carrying out filtration after stopping generating a precipitate; discarding the filtrate and washing and drying a filter cake, thus obtaining butoconazole nitrate. In the method provided by the invention, the conditions and parameters in the synthetic process are comprehensively and preferentially selected, and the impurities which are likely to be introduced in the production process are effectively controlled, thus increasing the production efficiency and the purity and yield of the product. Therefore, the method is more suitable for large-scale industrial production.

The invention discloses a method for preparing 1-chloro-4-(4-chlorophenyl)-2-tutanol comprising reacting a compound of formula III with magnesium to prepare a grignard reagent at a proper temperature in one or several non protonic solvents, then reacting the grignard reagent with a compound of formula IV. The 1-chloro-4-(4-chlorophenyl)-2-tutanol is an important intermediate for preparing butoconazole nitrate.

The invention provides a method for industrial production of a butoconazole nitrate intermediate, that is 1-chloro-4-p-chlorophenyl-2-butanol (a compound in formula II). The method of the invention comprises: 1. a Grignard reaction, that is, adopting p-chlorobenzyl chloride as a raw material, and performing a Grignard reaction with magnesium powder in a mixed solvent of methyl tertiary butyl ether and tetrahydrofuran; 2. a condensation reaction, that is, continuing reaction by adding epichlorohydrin to obtain the compound II which is an important intermediate for preparing butoconazole nitrate. According to the method, the raw materials are cheap and easily available, the reaction solvent is safer, and the method is suitable for industrial production.

The invention relates to a method for industrially synthesizing a butoconazole nitrate intermediate. The method comprises steps as follows: (1), imidazole and sodium hydride are taken as raw materials, are heated and stirred in a DMF (dimethyl formamide) solution and are cooled after sufficient reaction, 1-chlorine-4-(4-chlorphenyl)-2-butanol is slowly dropwise added, the mixture is heated, stirred and cooled after sufficient reaction, and a reaction liquid is obtained; (2), n-hexane and ice water are sequentially added to the reaction liquid obtained in the step (1), sufficiently stirred and filtered after sediment separation stops, a filter cake is washed, centrifugally dried and recrystallized with ethyl acetate and activated carbon, and the butoconazole nitrate intermediate is obtained. According to the provided method, conditions and parameters in the synthesis process are comprehensively and preferentially selected, the purity and yield of products are improved, and the method is more suitable for large-scale industrial production.

The invention relates to a method for industrial production of butoconazole nitrate. The method comprises the following steps that firstly, 1-(2-chlorine-4-(4-chlorphenyl)butyl)-1 hydrogen-imidazole is mixed with 2,6-dichoribenzene thiophenol, anhydrous potassium carbonate and acetone, a heating reflux reaction is carried out, anhydrous potassium carbonate is supplemented, the heating reflux reaction is continued, cooling and filtering are carried out, and concentrate is obtained after filter liquor is concentrated; secondly, extract liquor containing diethyl ether and water is added in the concentrate, after sufficient extraction is carried out, a water phase is discarded, and an organic phase is reserved; thirdly, concentrated nitric acid is dripped into the obtained organic phase on ice bath and stirring conditions, and filtering is carried out when sediment stops being generated; the filter liquor is discarded, a filter cake is washed with diethyl ether and acetone in sequence, and the metric acid butoconazole is obtained after the filter cake is dried. According to the method, conditions and parameters in the synthesizing process are comprehensively optimized, impurities likely to be introduced in the production process are effectively controlled, the production efficiency is improved, the purity and yield of products are increased, and the method is more suitable for large-scale industrial production.