US 12,492,165 B2 · Method for purifying key intermediates of citalopram

Abstract

The present invention relates to a method for purifying key intermediates of Citalopram, i.e. 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile and a salt thereof. The method comprises dissolving crude 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile (compound of formula I containing formaldehyde impurity) with an organic solvent, adding a washing solution, controlling the temperature, stirring, leaving to stand for layering, and removing the aqueous layer, so as to obtain a purified organic solution of 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile. The method provided by the present invention can effectively remove aldehyde group-containing impurities in the intermediate. The method of the present invention has the advantages of simple operation, cheap raw materials and mild conditions, and is suitable for large-scale industrial production.

Claims19

Dependent claims

A purification method for 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile, comprising the steps of:

dissolving a crude 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile in an organic solvent to obtain an organic solution of dissolved 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile;
adding an aqueous washing solution to the organic solution, and under a controlled temperature, stirring, standing and layering the mixed solution, and removing the aqueous layer to obtain a purified organic solution of 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile;
and
concentrating the purified organic solution to dryness to obtain a purified 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile.

1 more element

A purification method for 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile hydrochloride, comprising:

1) dissolving a crude 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile hydrochloride, adding liquid caustic soda to adjust pH, stirring the mixture to dissolve, standing and layering the thus obtained solution, and removing the aqueous layer to obtain an organic solution of dissolved 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile;
2) adding an aqueous washing solution to the organic solution of dissolved 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile in step 1), and under a controlled temperature, stirring, standing and layering the mixed solution, and removing the aqueous layer to obtain a purified organic solution of 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile;
and
3) adding a hydrochloric acid solution to the purified organic solution of 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile to adjust pH, and layering, filtering the mixture and adding with acetone, purifying the resultant by trituration, and drying the product to obtain a purified 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-hydroxymethylbenzonitrile hydrochloride.

1 more element

Dependencies are inferred from the claim text.

Method for purifying key intermediates of citalopram

Life of this patent

Method for purifying key intermediates of citalopram

Life of this patent

Abstract

Claims19