Abstract: A method for preparing voriconazole L-camphorsulphonate and voriconazole. The method for preparing voriconazole L-camphorsulphonate comprises: method 1: dissolving (2R,3S)/(2S,3R) isomer mixture and L-camphor sulphonic acid in water and acetone, and performing crystallisation filtration to obtain voriconazole L-camphorsulphonate; method 2: (a) dissolving a mixture of isomer mixture and L-camphor sulphonic acid in a first solvent and then performing crystallisation filtration; or (a?) dissolving L-camphorsulphonate of the isomer mixture in a first solvent and then performing crystallisation filtration; (b) concentrating the filtrate obtained in step (a) or (a?) into a solid; and (c) dissolving the solid obtained in step (b) in a second solvent and performing crystallisation filtration to obtain voriconazole L-camphorsulphonate. Adjusting the resolution solvent effectively reduces production costs and facilitates recycling of the resolution solvent.

Abstract: Disclosed is a preparation method for triphenylchloromethane, comprising the following steps: adding hydrochloric acid or a mixture of hydrochloric acid and Lewis acid to a mixture of triphenylmethanol and an organic solvent; stirring for reaction; removing the water layer after the completion of reaction to obtain an organic solution containing triphenylchloromethane. In the method, the conversion rate of triphenylmethanol is almost quantitative to be above 99%, and the content of triphenylchloromethane in the product obtained is above 99%. The operation is simple, and no waste gas is generated. Therefore, the method is environmentally friendly and suitable for industrialized production and can achieve better economic benefits.

Abstract: A synthesis method for a candesartan cilexetil intermediate represented by formula (II) is provided. The method includes (1) dissolving a compound represented by formula (IV) to an aprotic solvent to obtain a first mixed solution, and dissolving a phase transfer catalyst and an azidation reagent to water to obtain a second mixed solution; (2) dropping the first mixed solution to the second mixed solution for azidation reaction, and after the reaction is ended, standing and layering same to obtain an organic phase containing a compound represented by formula (V); (3) dropping the obtained organic phase containing the compound represented by formula (V) to tertiary butyl alcohol for rearrangement reaction, and after the reaction is ended, concentrating same to obtain a solid or oily material, then adding a crystallizing solvent to the obtained solid or oily material for recrystallization, and separating same to obtain a crystal.

Abstract: A method for preparing voriconazole L-camphorsulphonate and voriconazole. The method for preparing voriconazole L-camphorsulphonate comprises: method 1: dissolving (2R,3S)/(2S,3R) isomer mixture and L-camphor sulphonic acid in water and acetone, and performing crystallisation filtration to obtain voriconazole L-camphorsulphonate; method 2: (a) dissolving a mixture of isomer mixture and L-camphor sulphonic acid in a first solvent and then performing crystallisation filtration; or (a?) dissolving L-camphorsulphonate of the isomer mixture in a first solvent and then performing crystallisation filtration; (b) concentrating the filtrate obtained in step (a) or (a?) into a solid; and (c) dissolving the solid obtained in step (b) in a second solvent and performing crystallisation filtration to obtain voriconazole L-camphorsulphonate. Adjusting the resolution solvent effectively reduces production costs and facilitates recycling of the resolution solvent.

Abstract: Provided is a method for purifying ropinirole hydrochloride (4-2-di-n-propylaminoethyl-1,3-dihydro-2H-indole-2-ketohydrochloride). The method comprises: adding ropinirole hydrochloride containing a monopropyl impurity A into water, adding organic solvent, stirring and dissolving at room temperature, adding alkali, stirring, standing, demixing, and removing an aqueous layer; optionally, drying the organic layer by using anhydrous magnesium sulfate, and filtering; and adding acyl chloride or acid anhydride into the organic layer, stirring, concentrating the organic layer to be dry, adding an organic solvent into the obtained oily matter, adding concentrated hydrochloric acid, and stirring, so as to obtain the ropinirole hydrochloride. By using the method, the impurity A in the ropinirole hydrochloride can be effectively removed, and the ropinirole hydrochloride can be obtained with a high yield and a high purity, so that the impurity A is controlled and the purity of the product reaches a medicinal standard.

Abstract: Provided is a method for purifying ropinirole hydrochloride (4-2-di-n-propylaminoethyl-1,3-dihydro-2H-indole-2-ketohydrochloride). The method comprises: adding ropinirole hydrochloride containing a monopropyl impurity A into water, adding organic solvent, stirring and dissolving at room temperature, adding alkali, stirring, standing, demixing, and removing an aqueous layer; optionally, drying the organic layer by using anhydrous magnesium sulfate, and filtering; and adding acyl chloride or acid anhydride into the organic layer, stirring, concentrating the organic layer to be dry, adding an organic solvent into the obtained oily matter, adding concentrated hydrochloric acid, and stirring, so as to obtain the ropinirole hydrochloride. By using the method, the impurity A in the ropinirole hydrochloride can be effectively removed, and the ropinirole hydrochloride can be obtained with a high yield and a high purity, so that the impurity A is controlled and the purity of the product reaches a medicinal standard.

Abstract: Provided is a synthesis method for a voriconazole intermediate condensate as shown in formula II or an acid addition salt thereof. As shown in reaction formula 1, the product is prepared via compounds III and IV. The synthesis method adjusts the feeding means, and the reaction conditions are mild and controllable, thereby reducing the production of impurity A, avoiding the use of highly toxic metal lead, and eliminating the risk of highly toxic metal remaining in a drug. The product has a higher purity and significant industrial application value.

Abstract: Provided is a method for resolution of formula 4-[4-dimethylamino-1-(4-fluorophenyl)-1-hydroxylbutyl]-3-hydroxy-methyl benzonitrile as an enantiomer thereof, comprising the following steps: a salt of (S)-4-[4-dimethylamino-1-(4-fluorophenyl)-1-hydroxylbutyl]-3-hydroxymethyl benzonitrile with a resolving agent D-(+)di-p-toluoyl tartaric acid was crystallized in a resolving solvent; the method is characterized in that the resolving solvent is an ether solvent. Also provided is a new crystal form of the resolved intermediate.

Abstract: Provided is a method for resolution of formula 4-[4-dimethylamino-1-(4-fluorophenyl)-1-hydroxylbutyl]-3-hydroxy-methyl benzonitrile as an enantiomer thereof, comprising the following steps: a salt of (S)-4-[4-dimethylamino-1-(4-fluorophenyl)-1-hydroxylbutyl]-3-hydroxymethyl benzonitrile with a resolving agent D-(+)di-p-toluoyl tartaric acid was crystallized in a resolving solvent; the method is characterized in that the resolving solvent is an ether solvent. Also provided is a new crystal form of the resolved intermediate.

Abstract: Provided is a method for resolution of formula 4-[4-dimethylamino-1-(4-fluorophenyl)-1-hydroxylbutyl]-3-hydroxy-methyl benzonitrile as an enantiomer thereof, comprising the following steps: a salt of (S)-4-[4-dimethylamino-1-(4-fluorophenyl)-1-hydroxylbutyl]-3-hydroxymethyl benzonitrile with a resolving agent D-(+)di-p-toluoyl tartaric acid was crystallized in a resolving solvent; the method is characterized in that the resolving solvent is an ether solvent. Also provided is a new crystal form of the resolved intermediate.

Abstract: The present invention relates to a method for preparing a citalopram diol represented by formula IV, comprising the following steps: in the existence of an auxiliary reagent of metal salt, allowing 5-cyanophthalide to sequentially subjected to Grignard addition reactions with p-fluorophenyl magnesium halide and N, N-dimethylaminopropyl magnesium halide in an organic solvent; and after the reactions are completed, performing hydrolysis and separation to obtain citalopram diol represented by formula IV. In the present invention, by adding an auxiliary reagent of metal salt, the activity and the selectivity of the Grignard reactions are remarkably improved, and the reaction yield is obviously enhanced.

Abstract: Provided is a synthesis method for a voriconazole intermediate condensate as shown in formula II or an acid addition salt thereof. As shown in reaction formula 1, the product is prepared via compounds III and IV. The synthesis method adjusts the feeding means, and the reaction conditions are mild and controllable, thereby reducing the production of impurity A, avoiding the use of highly toxic metal lead, and eliminating the risk of highly toxic metal remaining in a drug. The product has a higher purity and significant industrial application value.

Abstract: The present invention relates to a method for preparing a citalopram diol represented by formula IV, comprising the following steps: in the existence of an auxiliary reagent of metal salt, allowing 5-cyanophthalide to sequentially subjected to Grignard addition reactions with p-fluorophenyl magnesium halide and N, N-dimethylaminopropyl magnesium halide in an organic solvent; and after the reactions are completed, performing hydrolysis and separation to obtain citalopram diol represented by formula IV. In the present invention, by adding an auxiliary reagent of metal salt, the activity and the selectivity of the Grignard reactions are remarkably improved, and the reaction yield is obviously enhanced.

Abstract: The present invention uses a candesartan cyclic compound as a starting material and performs thereon a three-step reaction of forming tetrazole, hydrolysis and adding a protecting group to directly obtain trityl candesartan without separating an intermediate product via crystallization. The operating process is simple and thus is more applicable to industrial production.

Abstract: Provided is a method for resolution of formula 4-[4-dimethylamino-1-(4-fluorophenyl)-1-hydroxylbutyl]-3-hydroxy-methyl benzonitrile as an enantiomer thereof, comprising the following steps: a salt of (S)-4-[4-dimethylamino-1-(4-fluorophenyl)-1-hydroxylbutyl]-3-hydroxymethyl benzonitrile with a resolving agent D-(+)di-p-toluoyl tartaric acid was crystallized in a resolving solvent; the method is characterized in that the resolving solvent is an ether solvent. Also provided is a new crystal form of the resolved intermediate.