Methanol → Bazedoxifene Acetate

Participants

Reaction Conditions

Reaction Steps

Crystalline bazedoxifene free base (35 g) is charged in a mixture of methanol (420 mL) and isopropyl alcohol (280 mL) and heated to reflux temperature to make a clear solution. The solution is filtered, cooled to about 38° C., followed by addition of acetic acid (5.8 g), and then seed crystals of Form D (1.75 g) are added. Then the mixture is allowed to cool to 0° C. over a period of about 2 hours. The solid is collected by filtration, washed with precooled methanol (70 mL), and dried under vacuum at about 65° C. for 5 hours to afford the title compound having HPLC Purity of 99.70%. The obtained compound has PSD as D90=61.97 microns, D50=13.52 microns and D10=3.45 microns and specific surface area of 1.72 m2/g. The sample is subjected to micronization to afford compound having D90=5.97 microns, D50=2.90 microns and D10=1.11 microns and specific surface area of 4.56 m2/g.

Provenance & Evidence