Methanol → Bazedoxifene Acetate

HRID 1503342Notes

Reaction equation

HRID 1503342 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 (15 g) is charged in a mixture of methanol (180 mL) and isopropyl alcohol (120 mL) and heated to reflux temperature to make a clear solution. The solution is filtered and cooled to about 25-30° C. over a period of 15 minutes followed by addition of acetic acid (1.91 g) and then seed crystals of Form D (0.75 g). Then the mixture is maintained at same temperature for about 20 minutes and then allowed to cool to 0° C. over a period of about 30 minutes. The solid is collected by filtration and dried under vacuum at about 80° C. for about 5 hours to afford the title compound having HPLC Purity of 99.80%. The obtained sample is analyzed by Scanning Electron Microscope and the image is depicted in FIG. 8.

Workup

  1. temperatureheated
  2. temperatureto reflux temperature
  3. filtrationThe solution is filtered
  4. additionfollowed by addition of acetic acid (1.91 g)
  5. temperatureThen the mixture is maintained at same temperature for about 20 minutes
  6. temperatureto cool to 0° C. over a period of about 30 minutes
  7. filtrationThe solid is collected by filtration
  8. customdried under vacuum at about 80° C. for about 5 hours

Sources & evidence

ORD record
ord-ce671af4707a45a490e0fbaae564861c
Source dataset
uspto-grants-2015_12
Patent number
US09212172B2

Reaction notes

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