Darifenacin Dehydro Impurity → Darifenacin

HRID 2253896Notes

Reaction equation

HRID 2253896 reaction equation
[C:1]([C:4]([C@@H:17]1[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][C:24]2[CH:25]=[CH:26][C:27]3[O:31][CH:30]=[CH:29][C:28]=3[CH:32]=2)[CH2:18]1)([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)(=[O:3])[NH2:2]>C(O)(=O)C.[Pd]>[C:1]([C:4]([C@@H:17]1[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][C:24]2[CH:25]=[CH:26][C:27]3[O:31][CH2:30][CH2:29][C:28]=3[CH:32]=2)[CH2:18]1)([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)(=[O:3])[NH2:2]

Participants

4

Reactant 1

HCID 22842830Darifenacin Dehydro Impurity

Product 1

HCID 444031Darifenacin

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent

Procedure

10% Palladium-on-carbon (10 mg) was added to a solution of 3-(S)-(-)-(1-carbamoyl-1,1-diphenylmethyl)-1-[2-(benzofuran-5-yl)-ethyl]pyrrolidine (0.1 g-see Example 7) in acetic acid (2 ml) and the mixture was hydrogenated at 40° C. and atmospheric pressure for 6 hours. The catalyst was filtered off and washed with water (20 ml). The combined filtrate and washings were transferred to a separating funnel, dichloromethane (20 ml) was added, and the mixture was basified by the addition of 10% aqueous sodium hydroxide. The layers were separated and the aqueous layer was further extracted with dichloromethane (3×30 ml). The combined dichloromethane extracts were dried (MgSO4) and concentrated in vacuo to give a colourless solid which was purified by column chromatography on silica eluting with dichloromethane containing methanol (4%). The product-containing fractions were combined and concentrated in vacuo to give the title compound as a colourless glass, yield 0.048 g, which was characterised spectroscopically to be identical to the product of Example 1 (B).

Workup

  1. customwas hydrogenated at 40° C.
  2. filtrationThe catalyst was filtered off
  3. washwashed with water (20 ml)
  4. customThe combined filtrate and washings were transferred to a separating funnel
  5. additiondichloromethane (20 ml) was added
  6. additionthe mixture was basified by the addition of 10% aqueous sodium hydroxide
  7. customThe layers were separated
  8. extractionthe aqueous layer was further extracted with dichloromethane (3×30 ml)
  9. dry with materialThe combined dichloromethane extracts were dried (MgSO4)
  10. concentrationconcentrated in vacuo
  11. customto give a colourless solid which
  12. customwas purified by column chromatography on silica eluting with dichloromethane
  13. additioncontaining methanol (4%)
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cc78109ef4fc4347bc9f27613e1af24f
Source dataset
uspto-grants-1993_08
Patent number
US05233053

Reaction notes

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