Methanol → Bazedoxifene Acetate

HRID 1503339Notes

Reaction equation

HRID 1503339 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 °C

Procedure

Crystalline bazedoxifene free base (10 g) is charged in a mixture of methanol (120 mL) and isopropyl alcohol (50 mL) and heated to reflux temperature to make a clear solution. The solution is filtered and cooled to about 27° C. over a period of 15 minutes followed by addition of acetic acid (1.65 g) and then seed crystals of Form D (0.5 g). Then the mixture is further allowed to cool to 0° C. over a period of about 2 hours. The reaction mixture is maintained at the same temperature for 1 hour and the solid is collected by filtration, washed with precooled methanol (20 mL), and dried under vacuum at about 70° C. for about 6 hours to afford the title compound having HPLC Purity of 99.84%.

Workup

  1. temperatureheated
  2. temperatureto reflux temperature
  3. filtrationThe solution is filtered
  4. additionfollowed by addition of acetic acid (1.65 g)
  5. temperatureto cool to 0° C. over a period of about 2 hours
  6. temperatureThe reaction mixture is maintained at the same temperature for 1 hour
  7. filtrationthe solid is collected by filtration
  8. washwashed with precooled methanol (20 mL)
  9. customdried under vacuum at about 70° C. for about 6 hours

Sources & evidence

ORD record
ord-4b9b95e46c9b4d3ca5edf16e460927c1
Source dataset
uspto-grants-2015_12
Patent number
US09212172B2

Reaction notes

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