Methanol → Bazedoxifene Acetate

HRID 1503329Notes

Reaction equation

HRID 1503329 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]>C(O)(C)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.[CH3:27][C:26]([OH:37])=[O:25]

Participants

4

Reactant 2

HCID 887MethanolHCID 154257Bazedoxifene

Product 1

HCID 154256Bazedoxifene Acetate

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
27.5 °C

Procedure

Crystalline bazedoxifene free base (20 g) is charged in a mixture of methanol (200 mL) and isopropyl alcohol (200 mL) and 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 (3.31 g). The reaction mixture is stirred for 15-30 minutes and subsequently seed crystals of Form D (1 g) are added and further the mixture is stirred at the same temperature for about 30 minutes. The reaction mixture is then cooled to 0-5° C. over a period of 30 minutes and stirred at the same temperature for 15-30 minutes. The solid is collected by filtration and washed with pre-cooled mixture of methanol (10 mL) and isopropyl alcohol (10 mL), and dried under vacuum at about 90° C. for 5-8 hours to afford the title compound.

Workup

  1. temperatureheated
  2. temperatureat reflux temperature
  3. filtrationThe solution is filtered
  4. additionfollowed by addition of acetic acid (3.31 g)
  5. additionsubsequently seed crystals of Form D (1 g) are added
  6. stirringfurther the mixture is stirred at the same temperature for about 30 minutes
  7. temperatureThe reaction mixture is then cooled to 0-5° C. over a period of 30 minutes
  8. stirringstirred at the same temperature for 15-30 minutes
  9. filtrationThe solid is collected by filtration
  10. washwashed
  11. temperaturewith pre-cooled
  12. additionmixture of methanol (10 mL) and isopropyl alcohol (10 mL)
  13. customdried under vacuum at about 90° C. for 5-8 hours

Sources & evidence

ORD record
ord-d5d63a6757b740b3898495eda5730085
Source dataset
uspto-grants-2015_12
Patent number
US09212172B2

Reaction notes

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