3-(S)-(+)-(1-carbamoyl-1,1-diphenylmethyl)pyrrolidine Tartrate → Darifenacin

HRID 2118061Notes

Reaction equation

HRID 2118061 reaction equation
[C:1]([CH:4]([CH:6]([C:8]([OH:10])=O)O)O)(O)=O.[C:11]([C:14]([C@@H:27]1[CH2:31][CH2:30][NH:29][CH2:28]1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=[O:13])[NH2:12]>C(O)(=O)C.[Pd]>[C:11]([C:14]([C@@H:27]1[CH2:31][CH2:30][N:29]([CH2:23][CH2:22][C:21]2[CH:14]=[CH:15][C:16]3[O:10][CH2:8][CH2:6][C:4]=3[CH:1]=2)[CH2:28]1)([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=[O:13])[NH2:12]

Participants

4

Reactant 1

HCID 186544563-(S)-(+)-(1-carbamoyl-1,1-diphenylmethyl)pyrrolidine Tartrate

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-370a6c00ad89453d8ca5c6a96f41e09e
Source dataset
uspto-grants-2008_10
Patent number
US07442806B2

Reaction notes

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