DNT-maleate and methods of preparation thereof

A process for preparing a pharmaceutically acceptable salt of duloxetine, comprising combining DNT, a solvent selected from the group consisting of C1-8 alcohols, C3-7 esters, C3-8 ethers, C3-7 ketones, C6-12 aromatic hydrocarbons, acetonitrile, water and mixtures thereof with maleic acid to form a reaction mixture, precipitating DNT-maleate from the reaction mixture, optionally recrystallizing the DNT maleate from ethyl acetate, converting the DNT maleate to DNT, converting the DNT to duloxetine, and converting the duloxetine to the pharmaceutically acceptable salt of duloxetine.

A crystalline form of DNT-maleate:

• characterized by a powder XRD pattern with peaks at about 9.4°, 14.0°, 18.7°, 23.3°, and 24.9° 2θ±0.2°2θ.

A crystalline form of DNT-maleate:

• characterized by a powder XRD pattern with peaks at about 14.4°, 18.5°, 23.1°, 27.2°, and 31.3° 2θ±0.2° 2θ.

A crystalline form of DNT maleate:

• characterized by a powder XRD pattern with peaks at about 9.4°, 18.7°, 23.4°, and 25.3° 2θ±0.2° 2θ.

A process for preparing a pharmaceutically acceptable salt of duloxetine, comprising combining DNT, a solvent selected from the group consisting of C1-8 alcohols, C3-7 esters, C3-8 ethers, C3-7 ketones, C6-12 aromatic hydrocarbons, acetonitrile, water and mixtures thereof with maleic acid to form a reaction mixture, precipitating DNT-maleate from the reaction mixture, recrystallizing the DNT maleate from ethyl acetate, converting the DNT maleate to DNT, converting the DNT to duloxetine, and converting the duloxetine to the pharmaceutically acceptable salt of duloxetine.

A process for lowering the content of R enantiomer present in DNT-maleate comprising recrystallizing DNT-maleate from an organic solvent and recovering the crystals.