219861-18-4

Upstream product

• 260371-16-2 4-(4-fluorobenzoyl)-3-(hydroxymethyl)benzonitrile 
• 19070-16-7 3-(N,N-dimethylamino)propylmagnesium chloride 
• 82104-74-3 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile 
• 460-00-4 1-Bromo-4-fluorobenzene 
• 123-20-6 vinyl n-butyrate 
• 103146-25-4 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile 
• 75-98-9 Trimethylacetic acid 
• 128173-53-5 (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile hemi-(+)-di-(p-toluoyl) tartaric acid salt 
• 674806-15-6 (+/-)-3-(acetoxymethyl)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]benzonitrile 
• 108-05-4 vinyl acetate 
• 21739-93-5 2-bromo-5-chlorobenzoic acid 
• 3874-54-2 4-(4-fluorophenyl)-4-oxo-n-butyl chloride 
• 60666-70-8 2-bromo-5-chlorobenzyl alcohol 
• 557-21-1 zinc(II) cyanide 

Downstream Products

• 128173-53-5 4-(1S)-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile (+)-di-(p-toluoyl)tartaric acid 
• 372941-54-3 3-oxocitalopram 

Relevant academic research and scientific papers

Method for preparing S-citalopram from R-diol

The invention provides a method for preparing S-citalopram from R-diol, and the method comprises two steps: chlorination reaction of adding a chlorinating agent into R-diol and cyclization reaction of adding metal hydroxide into S-dichloro oily matter. Compared with the prior art, the method has the advantages that the waste R-diol is recycled to prepare the S-citalopram, so that the production cost is reduced, the environmental pollution is reduced, and the atom economy is improved.

Synthesis method of citalopram intermediate

The invention provides a preparation method of a citalopram intermediate 4-(4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl) benzonitrile. The method provided by the invention has the advantages of cheap and easily available raw materials, short reaction steps, high yield, simple post-treatment, easy operation and the like, reduces the cost, has certain technical advantages,and is suitable for large-scale industrial production.

PROCESS FOR PRODUCING HYDROBROMIDE OF DIOL COMPOUND

PROBLEM TO BE SOLVED: To provide a method for producing 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile hydrobromide with a high purity and a high isolation yield. SOLUTION: Provided is a process for producing 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile hydrobromide characterized in bringing 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile and hydrogen bromide into contact in a mixed solvent of an ester-based solvent and water. SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT

Preparation method of high-optical-purity escitalopram oxalate intermediate S-configuration diol

The invention discloses a preparation method of an escitalopram oxalate intermediate S-configuration diol. The preparation method comprises the following steps: (1) carrying out hydrobromic acid salinization on racemic diol (4-(4-dimethylamino-1-p-fluorophenyl-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile) to obtain free racemic diol; and (2) carrying out chiral resolution on the free racemic diolby using (+)-di-p-toluoyl-D-tartaric acid in isopropanol by adopting a standing resolution mode, and conducting crystallization to obtain an escitalopram oxalate intermediate S-configuration diol crude product, and carrying out recrystallization refining on the crude product in an organic solvent to obtain the escitalopram oxalate intermediate with high optical purity. The method disclosed by theinvention is high in resolution efficiency and high in product yield, and the prepared diol intermediate is high in optical purity and can meet the requirements of industrial production.

PRODUCTION METHOD OF (1S)-1-[3-(DIMETHYLAMINO)PROPYL]-1-(4-FLUOROPHENYL)-1,3-DIHYDROISOBENZOFURAN-5-CARBONITRILE OXALATE

PROBLEM TO BE SOLVED: To provide a (1S)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (escitalopram) oxalate having extremely high optical purity and extremely little residual solvent. SOLUTION: The following production method is used: (1S)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile oxalate, by 1 part by mass, is dissolved and heated in an organic solvent containing 8-15 parts by volume of ethanol, then the solution is cooled at a rate of at least 25°C/h or more to crystallize so as to obtain the oxalate as a crystallized product. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT

PRODUCTION METHOD OF (1S)-4-[4-(DIMETHYLAMINO)-1-(4'-FLUOROPHENYL)-1-HYDROXYBUTYL]-3-(HYDROXYMETHYL)-BENZONITRILE HEMI(+)-DI-(p-TOLUOYL) TARTRATE, AND PRODUCTION METHOD OF (1S)-1-[3-(DIMETHYLAMINO)PROPYL]-1-(4-FLUOROPHENYL)-1,3-DIHYDROISOBENZOFURAN-5-CARBONITRILE AND SALT THEREOF USING THE TARTRATE

PROBLEM TO BE SOLVED: To provide a (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile hemi(+)-di-(p-toluoyl) tartrate having extremely high optical purity, and escitalopram having extremely high optical purity and its salt obtained from the above tartrate. SOLUTION: A production method is used, in which a crude (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile hemi(+)-di-(p-toluoyl) tartrate is recrystallized in a mixture solvent of alcohol and water, with the content of the water being 3.0 to 15.0 mass% in the mixture solvent of the alcohol and water, so as to obtain a recrystallized material of the above tartrate having extremely high optical purity. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT

PRODUCTION METHOD OF S-4-[4-(DIMETHYLAMINO)-1-(4'-FLUOROPHENYL)-1-HYDROXYBUTYL]-3-(HYDROXYMETHYL)-BENZONITRILE, AND PRODUCTION METHOD OF (1S)-1-[3-(DIMETHYLAMINO)PROPYL]-1-(4-FLUOROPHENYL)-1,3-DIHYDROISOBENZOFURAN-5-CARBONITRILE AND SALT THEREOF USING THE COMPOUND

PROBLEM TO BE SOLVED: To provide a (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile having extremely high chemical purity and optical purity, and escitalopram having extremely high optical purity and its salt obtained from the above compound. SOLUTION: The following production method is used: (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile hemi(+)-di-(p-toluoyl) tartrate is made to react in a solvent comprising at least one sparingly water-soluble organic solvent selected from the group consisting of aromatic hydrocarbons and halogenated hydrocarbons, and water so as to obtain an educt of the tartrate. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT

PROCESS FOR PRODUCING (1S)-4-[4-(DIMETHYLAMINO)-1-(4'-FLUOROPHENYL)-1-HYDROXYBUTYL]-3-(HYDROXYMETHYL)-BENZONITRILE HEMI(+)-DI-(p-TOLUOYL) TARTARIC ACID SALT, AND PROCESS FOR PRODUCING (1S)-1-[3-(DIMETHYLAMINO)PROPYL]-1-(4-FLUOROPHENYL)-1,3-DIHYDRO-ISOBENZOFURAN-5-CARBO-NITRILE AND SALT THEREOF USING SAID TARTARIC ACID SALT

PROBLEM TO BE SOLVED: To provide a production process in which (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile hemi(+)-di-(p-toluoyl) tartaric acid salt that has extremely high chemical purity and optical purity is obtained in high yield. SOLUTION: Provided is a production process characterized in producing a tartaric acid salt as a crystallized product by reacting racemate 4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile with (+)-di-(p-toluoyl) tartaric acid to yield (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile hemi(+)-di-(p-toluoyl) tartaric acid salt and followed by carrying out crystallization of the tartaric acid salt with a solvent containing 1-butanol. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPO&INPIT

Synthesizing method of escitalopram intermediate and escitalopram intermediate thereof

The invention discloses a synthesizing method of an escitalopram intermediate and escitalopram intermediate thereof. The synthesizing method comprises the following steps of using a compound (2) and acompound (3) as starting raw materials, and performing asymmetric 1,2-addition reaction, so as to obtain an escitalopram intermediate compound (1), wherein a reaction formula is shown in the description. The synthesizing method has the characteristics that the route is novel, the operation is simple and convenient, the synthesizing yield rate is high, the product purity is good, the raw materialsare easy to obtain, the price is low, the synthesizing method is suitable for industrialized production, and the like; the synthesized escitalopram intermediate can provide an intermediate raw material for the preparation of escitalopram.

Asymmetric synthesizing method of escitalopram intermediate and escitalopram intermediate thereof

The invention discloses an asymmetric synthesizing method of an escitalopram intermediate. The asymmetric synthesizing method comprises the following steps of using a compound (2) and a compound (3) as initial raw materials, and performing asymmetric 1,2-addition reaction, so as to obtain an escitalopram intermediate compound (1), wherein a reaction formula is shown in the description. The asymmetric synthesizing method has the characteristics that the route is novel, the operation is simple and convenient, the synthesizing yield rate is high, the product purity is good, the raw materials areeasy to obtain, the price is low, the asymmetric synthesizing method is suitable for industrialized production, and the like; the synthesized escitalopram intermediate can provide an intermediate rawmaterial for the preparation of escitalopram.