Ethanol → Bazedoxifene Acetate

HRID 1503323Notes

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.[CH2:36]([OH:38])[CH3:37].C([O:42]C(C)C)(C)C>C(O)(=O)C>[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.[CH3:37][C:36]([OH:42])=[O:38]

Participants

Conditions

Temperature: 27.5 °C

Procedure

Bazedoxifene free base (2 g) and ethanol (4 mL) are mixed and stirred at 25-30° C. Acetic acid (2 mL) is added drop-wise and stirring is continued at the same temperature for 10 minutes. The mixture is cooled to 10-15° C., followed by drop-wise addition of diisopropyl ether (60 mL) and seed crystals (40 mg). The mixture is stirred at the same temperature for 10 minutes and the solid is collected by filtration, sequentially washed with diisopropyl ether (20 mL) and water (5 mL), and suction dried for 5 minutes. The obtained wet solid is dried under vacuum at 70° C. for about 4-5 hours to afford 1.7 g of crystalline bazedoxifene acetate Form D. HPLC purity=99.46%, moisture content=0.61%.

Workup

stirringstirring
temperatureThe mixture is cooled to 10-15° C.
stirringThe mixture is stirred at the same temperature for 10 minutes
filtrationthe solid is collected by filtration
washsequentially washed with diisopropyl ether (20 mL) and water (5 mL), and suction
customdried for 5 minutes
customThe obtained wet solid is dried under vacuum at 70° C. for about 4-5 hours

Sources & evidence

ORD record: ord-ecf9200eb16b4caa819a9830f13291c1
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09212172B2

Reaction notes

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