Methanol → Bazedoxifene Acetate

HRID 1503338Notes

Reaction equation

HRID 1503338 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
38 °C

Procedure

Crystalline bazedoxifene free base (35 g) is charged in a mixture of methanol (420 mL) and isopropyl alcohol (280 mL) and heated to reflux temperature to make a clear solution. The solution is filtered, cooled to about 38° C., followed by addition of acetic acid (5.8 g), and then seed crystals of Form D (1.75 g) are added. Then the mixture is allowed to cool to 0° C. over a period of about 2 hours. The solid is collected by filtration, washed with precooled methanol (70 mL), and dried under vacuum at about 65° C. for 5 hours to afford the title compound having HPLC Purity of 99.70%. The obtained compound has PSD as D90=61.97 microns, D50=13.52 microns and D10=3.45 microns and specific surface area of 1.72 m2/g. The sample is subjected to micronization to afford compound having D90=5.97 microns, D50=2.90 microns and D10=1.11 microns and specific surface area of 4.56 m2/g.

Workup

  1. temperatureheated
  2. temperatureto reflux temperature
  3. filtrationThe solution is filtered
  4. additionfollowed by addition of acetic acid (5.8 g)
  5. additionseed crystals of Form D (1.75 g) are added
  6. temperatureto cool to 0° C. over a period of about 2 hours
  7. filtrationThe solid is collected by filtration
  8. washwashed with precooled methanol (70 mL)
  9. customdried under vacuum at about 65° C. for 5 hours

Sources & evidence

ORD record
ord-583b06685a12426eaf61c4ebae002835
Source dataset
uspto-grants-2015_12
Patent number
US09212172B2

Reaction notes

Loading…