Ethanol → Bazedoxifene Acetate

HRID 1503321Notes

Reaction equation

HRID 1503321 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]>>[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:17])=[O:38]

Participants

3

Reactant 2

HCID 702EthanolHCID 154257Bazedoxifene

Product 1

HCID 154256Bazedoxifene AcetateYield 80%

Conditions

Temperature
60 °C

Procedure

Bazedoxifene free base (1 g) and ethanol (10 mL) are mixed and heated to 60° C. to produce a clear solution, which is then filtered. The filtrate is cooled to 25-35° C. and acetic acid (4 mL) is slowly added at the same temperature. The mixture is cooled to 10-15° C., followed by addition of diisopropyl ether (5 mL) and seed crystals (20 mg, obtained from a previous example), and then additional diisopropyl ether (55 mL). The mixture is stirred for solid formation. The solid is collected by filtration and sequentially washed with diisopropyl ether (10 mL) and water (5 mL), then is suction dried for 5 minutes. The wet solid is dried under vacuum at 70° C. for about 4-5 hours to afford 900 mg (about 80% yield) of crystalline bazedoxifene acetate Form D.

Workup

  1. customto produce a clear solution, which
  2. filtrationis then filtered
  3. temperatureThe filtrate is cooled to 25-35° C.
  4. additionacetic acid (4 mL) is slowly added at the same temperature
  5. temperatureThe mixture is cooled to 10-15° C.
  6. additionfollowed by addition of diisopropyl ether (5 mL) and seed crystals (20 mg
  7. filtrationThe solid is collected by filtration
  8. washsequentially washed with diisopropyl ether (10 mL) and water (5 mL)
  9. customdried for 5 minutes
  10. customThe wet solid is dried under vacuum at 70° C. for about 4-5 hours

Sources & evidence

ORD record
ord-67deb20b46df4ddba34d4662ec05bc6a
Source dataset
uspto-grants-2015_12
Patent number
US09212172B2

Reaction notes

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