Methanol → Bazedoxifene Acetate

HRID 1503331Notes

Reaction equation

HRID 1503331 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 about 1 hour followed by addition of seed slurry of Form D (providing 250 mg of Form D crystals in 5 mL of methanol). The reaction mixture is allowed to cool to 0-5° C. in 30 minutes and maintained at the same temperature for another 30-40 minutes. 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 slurry of Form D (providing 250 mg of Form D crystals in 5 mL of methanol)
  6. temperatureto cool to 0-5° C. in 30 minutes
  7. temperaturemaintained at the same temperature for another 30-40 minutes
  8. filtrationThe solid is collected by filtration
  9. washwashed with water (10 mL)
  10. customdried under vacuum at about 90° C.

Sources & evidence

ORD record
ord-bd40c32efdcb4cc8b7bafae98d88ad10
Source dataset
uspto-grants-2015_12
Patent number
US09212172B2

Reaction notes

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