Acetone → Bazedoxifene Acetate

HRID 1503322Notes

Reaction equation

HRID 1503322 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
47.5 °C

Procedure

Bazedoxifene free base (2 g) and acetone (20 mL) are mixed and heated to 45-50° C. to produce a clear solution, which is filtered. The filtrate is cooled to 25-35° C. and seed crystals (20 mg) are added, followed by drop-wise addition of acetic acid (0.26 g). n-Heptane (50 mL) is added drop-wise over 30 minutes. The formed solid is collected by filtration, sequentially washed with n-heptane (10 mL), and then suction dried for 5 minutes. The wet solid is dried under vacuum at 70° C. for about 4-5 hours to afford 1.5 g of crystalline bazedoxifene acetate Form D.

Workup

  1. customto produce a clear solution, which
  2. filtrationis filtered
  3. temperatureThe filtrate is cooled to 25-35° C.
  4. additionseed crystals (20 mg) are added
  5. additionfollowed by drop-wise addition of acetic acid (0.26 g)
  6. additionn-Heptane (50 mL) is added drop-wise over 30 minutes
  7. filtrationThe formed solid is collected by filtration
  8. washsequentially washed with n-heptane (10 mL)
  9. customsuction dried for 5 minutes
  10. customThe wet solid is dried under vacuum at 70° C. for about 4-5 hours

Sources & evidence

ORD record
ord-1151fb2c412b4f4b9862b2b8a5bf2039
Source dataset
uspto-grants-2015_12
Patent number
US09212172B2

Reaction notes

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