Toluene → Bazedoxifene

HRID 1503332Notes

Reaction equation

HRID 1503332 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 87.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
10 °C

Procedure

Bazedoxifene hydrochloride (20 g) and dimethylformamide (200 mL) are charged into a round bottomed flask and stirred for 10-15 minutes. To the reaction mixture, triethylamine (8 mL) and toluene (400 mL) are added and the mixture is stirred at room temperature for 10-20 minutes. Then two lots of water (40 mL and 860 mL) are sequentially added with intermittent stirring for 10-20 minutes and finally the reaction mixture is stirred for 5-6 hours at room temperature. 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 (40 mL), toluene (40 mL) and dried under vacuum below 50° C. to afford 16.2 g of crystalline bazedoxifene free base Form A of 99.79% HPLC purity.

Workup

  1. stirringthe mixture is stirred at room temperature for 10-20 minutes
  2. stirringwith intermittent stirring for 10-20 minutes
  3. stirringfinally the reaction mixture is stirred for 5-6 hours at room temperature
  4. stirringstirred at the same temperature for another 3-4 hours
  5. customThe solid formed
  6. filtrationis collected by filtration
  7. washwashed with water (40 mL), toluene (40 mL)
  8. customdried under vacuum below 50° C.

Sources & evidence

ORD record
ord-3e596fa4aaaa4b1bb0751a045aaf281d
Source dataset
uspto-grants-2015_12
Patent number
US09212172B2

Reaction notes

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