(S)—N,N-Dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine benzenesulfonate (DNT-benzenesulfonate) and polymorphs of DNT-benzenesulfonate, compositions of DNT-benzenesulfonate and its polymorphs, processes for the preparation of DNT-benzenesulfonate and its polymorphs, and processes for the preparation of duloxetine hydrochloride from DNT-benzenesulfonate are provided.
Description
BRIEF DESCRIPTION OF THE FIGURE
FIG. 1 illustrates the powder X-ray diffraction pattern for DNT-benzenesulfonate Form BSulfl.
Claims
1. A compound (DNT-benzenesulfonate) having the following formula:
2. The compound of claim 1, wherein the compound is isolated.
3. The compound of claim 2, wherein the compound is isolated as a crystal.
4. A process for preparing DNT-benzenesulfonate of claim 1, comprising combining DNT with benzenesulfonic acid to form a reaction mixture, precipitating DNT-benzenesulfonate from the reaction mixture and recovering the precipitate.
5. The process of claim 4 wherein the reaction mixture contains a solvent selected from the group consisting of C1-8 alcohols, C3-7 esters, C3-8 ethers, C6-12 aromatic hydrocarbons, acetonitrile, water, and mixtures thereof.
6. The process of claim 5, wherein the solvent is water.
7. 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 benzenesulfonic acid to form a reaction mixture, precipitating DNT-benzenesulfonate from the reaction mixture, converting the DNT-benzenesulfonate to DNT, converting the DNT to duloxetine, and converting the duloxetine to the pharmaceutically acceptable salt of duloxetine.
8. The process of claim 7, wherein the pharmaceutically acceptable salt of duloxetine is duloxetine HCl.
9. A crystalline form of DNT-benzenesulfonate:
10. The crystalline form of claim 9, further characterized by X-ray powder diffraction peaks at about 14.5°, 18.7°, 23.5°, 26.8°, and 28.1° 2θ±0.2° 2θ.
11. The crystalline form of claim 9 further characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 1.
12. The crystalline form of claim 9, wherein the crystalline form is present in a batch at a polymorphic purity level of at least about 50% by weight.
13. A process for preparing the crystalline form of claim 9 comprising combining benzenesulfonic acid with DNT in water to form a reaction mixture, precipitating the DNT-benzenesulfonate, and recovering the DNT-benzenesulfonate crystalline Form BSulfl.
14. The process of claim 13, wherein the process is carried out at about room temperature.
15. A process for preparing duloxetine hydrochloride comprising combining benzenesulfonic acid with DNT in water to form a reaction mixture, precipitating the DNT-benzenesulfonate, and converting the crystalline DNT-benzenesulfonate to duloxetine hydrochloride.
16. A process for preparing a pharmaceutically acceptable salt of duloxetine, comprising converting DNT-benzenesulfonate prepared by the process of claim 1 to the pharmaceutically acceptable salt of duloxetine.
17. The process of claim 16, wherein the pharmaceutically acceptable salt of duloxetine is duloxetine hydrochloride.
Patent Application
20070173540
