Succinate salt of O-desmethyl-venlafaxine
View Patent ↗A novel salt of O-desmethyl venlafaxine is provided, O-desmethylvenlafaxine succinate. Pharmaceutical compositions, dosage forms and methods of use are also provided.
1. A method of preparing O-desmethyl-venlafaxine comprising the step of demethylating venlafaxine or a salt thereof with an alkali metal salt of a trialkyl borohydride.
2. The method of claim 1 , wherein each alkyl group in the trialkyl borohydride is independently a C 1 –C 6 alkyl.
3. The method of claim 2 , wherein the alkali metal salt of a trialkyl borohydride is selected from L-selectride, K-selectride, lithium triethylborohydride, potassium triethylborohydride, and mixtures thereof.
4. The method of claim 3 , wherein the alkali metal salt of a trialkyl borohydride is L-selectride.
5. The method of claim 1 , wherein the demethylation step is performed at a temperature of from about 60 to about 140° C.
6. The method of claim 1 , further comprising the step of converting the O-desmethyl-venlafaxine to O-desmethyl-venlafaxine succinate.
7. The method of claim 1 , further comprising the step of deactivating any boron containing byproducts produced by the demethylation reaction.
8. The method of claim 7 , wherein the deactivating step comprises oxidizing the boron containing byproducts.
9. The method of claim 8 , wherein the oxidizing step comprises reacting the boron containing byproducts with an oxidizing agent selected from hydrogen peroxide, sodium perborate, and mixtures thereof.
10. The method of claim 8 , wherein the oxidizing step comprises adding the boron containing byproducts to an oxidizing agent or a solution comprising an oxidizing agent.
11. A method of preparing O-desmethyl-venlafaxine comprising the steps of:
(a) demethylating venlafaxine or a salt thereof with an alkali metal salt of a trialkyl borohydride to yield an alkali metal salt of O-desmethyl-venlafaxine; and
(b) converting the alkali metal salt of O-desmethyl-venlafaxine to the free base of O-desmethyl-venlafaxine.
12. The method of claim 11 , wherein step (b) comprises neutralizing the alkali metal salt of O-desmethyl-venlafaxine with acid.
13. The method of claim 11 , further comprising the step of (c) converting the free base of O-desmethyl-venlafaxine to O-desmethyl-venlafaxine succinate.
14. The method of claim 11 , wherein the venlafaxine in step (a) is the free base of venlafaxine.
15. The method of claim 1 wherein the demethylation step is performed at about 90° C.
16. The method of claim 1 wherein the demethylation step is performed with 5.5 molar excess of trialkyl borohydride.