Nafoxidine Hydrochloride → rac 7-Methoxy Lasofoxifene

HRID 1859081Notes

Reaction equation

HRID 1859081 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-d6882ab696eb4d80914040bf34878dce
Source dataset
uspto-grants-2000_11
Patent number
US06153622

Reaction notes

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