Nafoxidine Hydrochloride → rac 7-Methoxy Lasofoxifene

HRID 1532775Notes

Reaction equation

HRID 1532775 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[C:10]([C:14]1[CH:27]=[CH:26][C:17]([O:18][CH2:19][CH2:20][N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:16][CH:15]=1)=[C:9]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:8][CH2:7]2>CCO.CO.[OH-].[OH-].[Pd+2]>[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[C@@H:10]([C:14]1[CH:27]=[CH:26][C:17]([O:18][CH2:19][CH2:20][N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:16][CH:15]=1)[C@@H:9]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:8][CH2:7]2

Participants

5

Reactant 1

HCID 15805Nafoxidine Hydrochloride

Product 1

HCID 11373717rac 7-Methoxy LasofoxifeneYield 90.4%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

1-{2-[4-(6-Methoxy-2-phenyl-3,4-dihydronaphthalen-1-yl)phenoxy]ethyl}pyrrolidine hydrochloride (nafoxidene hydrochloride) (75 g, 162 mmol) was dissolved in 1000 mL of EtOH and 300 mL of MeOH. Dry Pd(OH)2 on carbon was added and the mixture was hydrogenated on a Parr shaker at 50° C. and 50 psi for 68 h. The catalyst was filtered off with the aid of celite and the solvents were removed in vacuo. The resulting white solid was dissolved in CH2Cl2 and the solution was washed with satd NaHCO3 (aq). The organic solution was dried (MgSO4), filtered, and concentrated to yield an off-white solid (62.6 g, 90%).

Workup

  1. customwas hydrogenated on a Parr shaker at 50° C.
  2. filtrationThe catalyst was filtered off with the aid of celite
  3. customthe solvents were removed in vacuo
  4. dissolutionThe resulting white solid was dissolved in CH2Cl2
  5. washthe solution was washed with satd NaHCO3 (aq)
  6. dry with materialThe organic solution was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-c1d3d463a6a54326954891332ae83885
Source dataset
uspto-grants-2001_03
Patent number
US06204286B1

Reaction notes

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