Isopropanol → Bazedoxifene Acetate

HRID 1503328Notes

Reaction equation

HRID 1503328 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.[CH:36]([OH:39])([CH3:38])C>CO>[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.[CH3:38][C:36]([OH:39])=[O:17]

Participants

4

Reactant 2

HCID 3776IsopropanolHCID 154257Bazedoxifene

Product 1

HCID 154256Bazedoxifene Acetate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

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. In a separate flask, slurry of crystalline Form D of bazedoxifene acetate is prepared by providing seed of Form D (250 mg) in methanol (5 mL). The said seed slurry is added to the previous reaction mixture and further it is cooled to 10-15° C. in a period of 30 minutes followed by addition of isopropyl alcohol in a period of 2 hours. The reaction mixture is further cooled to 0-5° C. and maintained at same temperature for 30-45 minutes. The solid is collected by filtration and sequentially washed with isopropyl alcohol (5 mL) and methanol (5 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. customIn a separate flask, slurry of crystalline Form D of bazedoxifene acetate is prepared
  6. additionThe said seed slurry is added to the previous reaction mixture and further it
  7. temperatureis cooled to 10-15° C. in a period of 30 minutes
  8. temperatureThe reaction mixture is further cooled to 0-5° C.
  9. temperaturemaintained at same temperature for 30-45 minutes
  10. filtrationThe solid is collected by filtration
  11. washsequentially washed with isopropyl alcohol (5 mL) and methanol (5 mL)
  12. customdried under vacuum at about 90° C.

Sources & evidence

ORD record
ord-a15e96dc9f594d0886a44ea23a677c43
Source dataset
uspto-grants-2015_12
Patent number
US09212172B2

Reaction notes

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