Acetone → Bazedoxifene Acetate

HRID 1503326Notes

Reaction equation

HRID 1503326 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[C:37]([CH3:39])=[O:38]>>[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.[CH3:39][C:37]([OH:17])=[O:38]

Participants

3

Reactant 2

HCID 180AcetoneHCID 154257Bazedoxifene

Product 1

HCID 154256Bazedoxifene Acetate

Conditions

Temperature
50 °C

Procedure

Bazedoxifene free base (18 g) and acetone (162 mL) are mixed and stirred at 45-55° C. to make a clear solution. The said solution is cooled to room temperature and filtered to make particle free. To the filtrate, seed crystals of bazedoxifene acetate (360 mg) are added at room temperature and mixture is cooled to 15-20° C. followed by addition of a solution of acetic acid (2.34 g) in acetone (18 mL) at the same temperature. To the mixture, heptane (486 mL) is added over a period of 5-10 minutes and mixture is stirred at 15-20° C. for solid formation. The solid so obtained is collected by filtration and washed with heptane (50 mL) and dried under vacuum at below 80° C. to afford 17.80 g of crystalline bazedoxifene acetate Form D. D90=76.17 microns; D10=3.58 microns, D50=33.59 microns. The material is subjected to micronization under nitrogen atmosphere with a pressure of 4 kg/cm2 to afford the particles with D90=12.32 microns; D10=1.11 microns, D50=4.19 microns.

Workup

  1. temperatureThe said solution is cooled to room temperature
  2. filtrationfiltered
  3. additionTo the filtrate, seed crystals of bazedoxifene acetate (360 mg) are added at room temperature
  4. temperaturemixture is cooled to 15-20° C.
  5. additionfollowed by addition of a solution of acetic acid (2.34 g) in acetone (18 mL) at the same temperature
  6. additionTo the mixture, heptane (486 mL) is added over a period of 5-10 minutes
  7. stirringmixture is stirred at 15-20° C. for solid formation
  8. customThe solid so obtained
  9. filtrationis collected by filtration
  10. washwashed with heptane (50 mL)
  11. customdried under vacuum at below 80° C.

Sources & evidence

ORD record
ord-f285d2fe3cb94b51a70e26a61fa97dfa
Source dataset
uspto-grants-2015_12
Patent number
US09212172B2

Reaction notes

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