Methanol → Bazedoxifene Acetate

HRID 1503327Notes

Reaction equation

HRID 1503327 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 AcetateYield 87%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
27.5 °C

Procedure

Crystalline bazedoxifene free base (60 g) is charged in a mixture of methanol (720 mL) and isopropyl alcohol (480 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 (9.94 g). The reaction mixture is stirred for 15-30 minutes and subsequently seed crystals of Form D (3 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 1 hour and stirred at the same temperature for 15-30 minutes. The solid is collected by filtration and washed with pre-cooled mixture of methanol (72 mL) and isopropyl alcohol (48 mL), and dried under vacuum at about 90° C. for 5-8 hours to afford the title compound in about 87% yield.

Workup

  1. temperatureheated
  2. temperatureat reflux temperature
  3. filtrationThe solution is filtered
  4. additionfollowed by addition of acetic acid (9.94 g)
  5. additionsubsequently seed crystals of Form D (3 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 1 hour
  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 (72 mL) and isopropyl alcohol (48 mL)
  13. customdried under vacuum at about 90° C. for 5-8 hours

Sources & evidence

ORD record
ord-f19ff33a80c54cbda43bf831ff2098f2
Source dataset
uspto-grants-2015_12
Patent number
US09212172B2

Reaction notes

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