Toluene → Bazedoxifene

HRID 1503341Notes

Reaction equation

HRID 1503341 reaction equation
[CH3:1][C:2]1[C:6]2[CH:7]=[C:8]([OH:11])[CH:9]=[CH:10][C:5]=2[N:4]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][N:22]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)=[CH:15][CH:14]=2)[C:3]=1[C:29]1[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=1.Cl.CN(C)C=O.C(N(CC)CC)C.C1(C)C=CC=CC=1>O>[CH3:1][C:2]1[C:6]2[CH:7]=[C:8]([OH:11])[CH:9]=[CH:10][C:5]=2[N:4]([CH2:12][C:13]2[CH:14]=[CH:15][C:16]([O:19][CH2:20][CH2:21][N:22]3[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]3)=[CH:17][CH:18]=2)[C:3]=1[C:29]1[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 6228DimethylformamideHCID 8471TriethylamineHCID 9936012Bazedoxifene HCl

Product 1

HCID 154257BazedoxifeneYield 88%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
30 °C

Procedure

Bazedoxifene hydrochloride (3 Kg), dimethylformamide (30 L), triethylamine (1.2 L), and toluene (60 L) are charged in a reactor and stirred for 10-20 minutes at 25-35° C. Then two lots of water (6 L and 129 L) are sequentially added with intermittent stirring for 10-20 minutes and finally the reaction mixture is stirred for 5-6 hours at 25-35° C. The reaction mixture is then cooled to 7.5-12.5° C. and stirred at the same temperature for another 3-4 hours. The solid formed is collected by filtration, washed with water (4 L), with toluene (4 L), and dried under vacuum at about 50° C. for 8 hours to afford crystalline bazedoxifene free base Form A in about 88% yield.

Workup

  1. stirringwith intermittent stirring for 10-20 minutes
  2. stirringfinally the reaction mixture is stirred for 5-6 hours at 25-35° C
  3. temperatureThe reaction mixture is then cooled to 7.5-12.5° C.
  4. stirringstirred at the same temperature for another 3-4 hours
  5. customThe solid formed
  6. filtrationis collected by filtration
  7. washwashed with water (4 L), with toluene (4 L)
  8. customdried under vacuum at about 50° C. for 8 hours

Sources & evidence

ORD record
ord-409da324f6064acda29003db059ac71d
Source dataset
uspto-grants-2015_12
Patent number
US09212172B2

Reaction notes

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