Methods of preparing polymorphic form A of bazedoxifene acetate

1. A method of preparing polymorphic Form A of bazedoxifene acetate, the method comprising: (a) contacting hexamethylenimino benzyloxyindole with hydrogen in a solvent comprising ethanol, and in the presence of a catalyst at elevated temperature to provide a first reaction mixture comprising bazedoxifene free base, wherein the first reaction mixture is substantially free from hexamethylenimino benzyloxyindole, wherein step (a) is completed in less than about 10 hours; (b) treating said first reaction mixture with an antioxidant to provide a second reaction mixture; (c) filtering said second reaction mixture to provide a solution comprising bazedoxifene free base; and (d) treating said solution with acetic acid to crystallize polymorphic Form A of bazedoxifene acetate.

2. The method of claim 1 , wherein in step (a), the solvent further comprises at least one solvent selected from the group consisting of ethyl acetate, acetone, cyclohexane and methanol.

3. The method of claim 1 , wherein step (a) is completed in less than about 4 hours.

4. The method of claim 1 , wherein in step (a), the catalyst is a Pd/C catalyst.

5. The method claim 4 , wherein the Pd/C catalyst used is in an amount (a) less than about 10 mmol per mmol of hexamethylenimino benzyloxyindole used.

6. The method of claim 4 , wherein the Pd/C catalyst has a total surface area (B.E.T) of more than about 1100 m 2 /g.

7. The method of claim 4 , wherein the Pd/C catalyst is non-reduced Pd on moist carbon.

8. The method of claim 1 , wherein step (a) is carried out at a temperature of about 30° C. or higher.

9. The method of claim 1 , wherein step (a) is carried out at a temperature of about 50° C.

10. The method of claim 1 , wherein in step (b), said antioxidant is selected from ascorbic acid, sodium ascorbate, ascorbyl palmitate, citric acid, propyl gallate, alpha Tocopherol (vitamin E), vitamin E TPGS, vitamin E acetate, butylated hydroxytoluene, butylated hydroxyanisole and mixtures thereof.

11. The method of claim 1 , wherein in step (b), said antioxidant is ascorbic acid.

12. The method of claim 1 , wherein step (d) is facilitated by seeding with polymorphic Form A of bazedoxifene acetate.

13. The method of claim 1 , wherein step (d) is carried out at a temperature of about 40° C. or lower.

14. The method of claim 1 , wherein step (d) is carried out at a temperature ranging from about 20° C. to about 35° C.

15. The method of claim 1 , wherein in step (d said polymorphic Form A of bazedoxifene acetate is more than 99% pure.

16. The method of claim 1 , further comprising isolating polymorphic Form A of bazedoxifene acetate by filtration, washing and drying.

17. The method of claim 16 , wherein said drying is conducted in an agitated filter dryer or a tumble dryer.