Methanol → Bazedoxifene Acetate

HRID 1503330Notes

Reaction equation

HRID 1503330 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.C[OH: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.[CH3:27][C:26]([OH:37])=[O:25]

Participants

3

Reactant 2

HCID 887MethanolHCID 154257Bazedoxifene

Product 1

HCID 154256Bazedoxifene Acetate

Conditions

Temperature
27.5 °C

Procedure

Crystalline bazedoxifene free base (5 g) is charged in methanol (100 mL) heated at reflux temperature to make a clear solution. The solution is filtered and cooled to 25-30° C. followed by addition of acetic acid (0.82 g). The reaction mixture is stirred for ˜1 hour followed by addition of seed crystals of Form D (250 mg). The reaction mixture is allowed to cool to 0-5° C. at which point water (200 mL) is slowly added over a period of 2 hours. The reaction mixture is maintained under stirring for another 1 hour at 0-5° C. The solid is collected by filtration and washed with water (10 mL), and dried under vacuum at about 90° C. to afford the title compound.

Workup

  1. temperatureheated
  2. temperatureat reflux temperature
  3. filtrationThe solution is filtered
  4. additionfollowed by addition of acetic acid (0.82 g)
  5. additionfollowed by addition of seed crystals of Form D (250 mg)
  6. temperatureto cool to 0-5° C. at which point water (200 mL)
  7. additionis slowly added over a period of 2 hours
  8. temperatureThe reaction mixture is maintained
  9. stirringunder stirring for another 1 hour at 0-5° C
  10. filtrationThe solid is collected by filtration
  11. washwashed with water (10 mL)
  12. customdried under vacuum at about 90° C.

Sources & evidence

ORD record
ord-69997a7cc1774fcb8183f7aedc149cce
Source dataset
uspto-grants-2015_12
Patent number
US09212172B2

Reaction notes

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