Methanol → Bazedoxifene Acetate

HRID 1503340Notes

Reaction equation

HRID 1503340 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 (1.7 Kg) is charged in a mixture of methanol (20.4 L) and isopropyl alcohol (13.6 L) and heated to reflux temperature to make a clear solution and stirred at same for 15-30 minutes. The solution is filtered and subsequently cooled to about 25-30° C. over a period of 10 minutes followed by addition of acetic acid (0.28 Kg) and seed crystals of Form D (85 g). Then the mixture is further allowed to cool to 0-5° C. over a period of about 20 minutes. The reaction mixture is maintained at the same temperature for 30-60 minutes and the solid is collected by filtration, washed with pre-cooled methanol (3.4 L), and dried under vacuum at about 60-65° C. to afford the title compound.

Workup

  1. temperatureheated
  2. temperatureto reflux temperature
  3. filtrationThe solution is filtered
  4. additionfollowed by addition of acetic acid (0.28 Kg) and seed crystals of Form D (85 g)
  5. temperatureto cool to 0-5° C. over a period of about 20 minutes
  6. temperatureThe reaction mixture is maintained at the same temperature for 30-60 minutes
  7. filtrationthe solid is collected by filtration
  8. washwashed with pre-cooled methanol (3.4 L)
  9. customdried under vacuum at about 60-65° C.

Sources & evidence

ORD record
ord-1ad8796e61ac4904911a4064b5eac8f0
Source dataset
uspto-grants-2015_12
Patent number
US09212172B2

Reaction notes

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