Methanol → Bazedoxifene Acetate

HRID 1503336Notes

Reaction equation

HRID 1503336 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 (35 g) is charged in a mixture of methanol (420 mL) and isopropyl alcohol (280 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 (5.8 g) and then seed crystals of Form D (1.75 g). Further the mixture is stirred at the same temperature for about 20 minutes. The reaction mixture is then cooled to 0-5° C. over a period of about 30 minutes and stirred at the same temperature for 15-30 minutes. The solid is collected by filtration, washed with methanol (70 mL), and dried under vacuum at about 80° 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 (5.8 g)
  5. temperatureThe reaction mixture is then cooled to 0-5° C. over a period of about 30 minutes
  6. stirringstirred at the same temperature for 15-30 minutes
  7. filtrationThe solid is collected by filtration
  8. washwashed with methanol (70 mL)
  9. customdried under vacuum at about 80° C. for 5-8 hours

Sources & evidence

ORD record
ord-c1d541b00ec044d0ab810daeb6c57d3a
Source dataset
uspto-grants-2015_12
Patent number
US09212172B2

Reaction notes

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