372941-48-5

Usage

Uses

Used in Pharmaceutical Industry:
1-(4-Fluorophenyl)-1,3-dihydro-3-oxo-5-isobenzofurancarbonitrile is used as an intermediate for the preparation of Citalopram, a widely prescribed antidepressant medication. Its role in the synthesis process is crucial for the production of the final drug product, which is used to treat major depressive disorder and other mood disorders.
As an intermediate, 1-(4-Fluorophenyl)-1,3-dihydro-3-oxo-5-isobenzofurancarbonitrile contributes to the development of Citalopram by participating in the chemical reactions that lead to the formation of the final compound. This application is significant because it enables the creation of an effective treatment for individuals suffering from depression and related conditions.

InChI:InChI=1/C15H8FNO2/c16-11-4-2-10(3-5-11)14-12-6-1-9(8-17)7-13(12)15(18)19-14/h1-7,14H

Synthetic route

1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile (64169-67-1) → 1-(4-fluorophenyl)-3-oxo-1,3-dihydroisobenzofuran-5-carbonitrile (372941-48-5)

Conditions	Yield
With 1,1'-bis-(diphenylphosphino)ferrocene; oxygen; diphenyldisulfane In 1,4-dioxane at 80℃; under 760.051 Torr; for 15h; Schlenk technique; regioselective reaction;	50%

1-(4-fluoro-phenyl)-3-oxo-1,3-dihydro-isobenzofuran-5-carboxylic acid amide (372941-46-3) → 1-(4-fluorophenyl)-3-oxo-1,3-dihydroisobenzofuran-5-carbonitrile (372941-48-5)

Conditions	Yield
In thionyl chloride; N,N-dimethyl-formamide	7.8 g (62%)

Upstream product

• 64169-67-1 1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile 
• 372941-46-3 1-(4-fluoro-phenyl)-3-oxo-1,3-dihydro-isobenzofuran-5-carboxylic acid amide 

Relevant academic research and scientific papers

Thiyl radical promoted iron-catalyzed-selective oxidation of benzylic sp3 C-H bonds with molecular oxygen

A ligand-free iron-catalyzed method for the oxygenation of benzylic sp3 C-H bonds by molecular oxygen (1 atm) using a thiyl radical as a cocatalyst has been developed. This transformation provides a facile access to amides, esters and ketones from readily accessible corresponding amines, ethers and alkanes. It features high regioselectivity, mild oxidative conditions and excellent functional group compatibility, providing good opportunities to the site-selective functionalization of complex molecules. Preliminary mechanistic studies suggest that this reaction may not undergo a benzylic cation intermediate pathway and the carbonyl oxygen atom in the products may be derived from molecular oxygen.

Method for the preparation of citalopram

A method for the preparation of citalopram comprising reaction of a compound of formula 5-aminomethyl-1-(3-dimethylamino-propyl)-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran with an oxidising agent to prepare citalopram.