Bazedoxifene Acetate → Bazedoxifene

HRID 1503313

Reaction equation

[CH3:1][C:2]1[C:3]2[CH:4]=[C:5]([OH:35])[CH:6]=[CH:7][C:8]=2[N:9]([CH2:18][C:19]2[CH:20]=[CH:21][C:22]([O:25][CH2:26][CH2:27][N:28]3[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)=[CH:23][CH:24]=2)[C:10]=1[C:11]1[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=1.CC(O)=O>CN(C)C=O>[CH3:1][C:2]1[C:3]2[CH:4]=[C:5]([OH:35])[CH:6]=[CH:7][C:8]=2[N:9]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][N:28]3[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]3)=[CH:21][CH:20]=2)[C:10]=1[C:11]1[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Bazedoxifene acetate (47 g) and dimethylformamide (235 mL) are mixed and heated to 80° C. to produce a clear solution, followed by filtration. To the filtrate, toluene (2700 mL), morpholine (3.0 mL), and water (1810 mL) are added and the mixture is stirred overnight at room temperature. The solid is collected by filtration, washed with toluene (70 mL) and water (70 mL), then dried under vacuum below 80° C. for about 6-8 hours to afford Form A of crystalline bazedoxifene free base: D90=49.80 microns; D10=3.61 microns, D50=25.30 microns. The material is subjected to micronization under nitrogen atmosphere with a pressure of 4 kg/cm2 to afford the particles with D90=6.04 microns; D10=0.89 microns, D50=2.37 microns.

Workup

customto produce a clear solution
filtrationfollowed by filtration
additionTo the filtrate, toluene (2700 mL), morpholine (3.0 mL), and water (1810 mL) are added
filtrationThe solid is collected by filtration
washwashed with toluene (70 mL) and water (70 mL)
customdried under vacuum below 80° C. for about 6-8 hours

Sources & evidence

ORD record: ord-eff699e8967c46adb4b8550d94e716c7
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09212172B2

Linked notes

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