Potassium Carbonate → (±)-Darifenacin

HRID 2253889Notes

Reaction equation

HRID 2253889 reaction equation
[C:1]([C:4]([CH:17]1[CH2:21][CH2:20][NH:19][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].Br[CH2:23][CH2:24][C:25]1[CH:26]=[CH:27][C:28]2[O:32][CH2:31][CH2:30][C:29]=2[CH:33]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[C:1]([C:4]([CH:17]1[CH2:21][CH2:20][N:19]([CH2:23][CH2:24][C:25]2[CH:26]=[CH:27][C:28]3[O:32][CH2:31][CH2:30][C:29]=3[CH:33]=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

5

Reactant 3

HCID 11430Potassium CarbonateHCID 136337542,2-Diphenyl-2-(pyrrolidin-3-yl)acetamideHCID 218311605-(2-Bromoethyl)-2,3-dihydro-1-benzofuran

Product 1

HCID 72054(±)-Darifenacin

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture containing 3-(R,S)-(1-carbamoyl-1,1-diphenylmethyl)pyrrolidine (0.33 g-see Preparation 8), 5-(2-bromoethyl)-2,3-dihydrobenzofuran (0.25 g-see Preparation 13), anhydrous potassium carbonate (0.3 g) and acetonitrile (10 ml) was heated under reflux for 2 hours. The mixture was partitioned between dichloromethane (50 ml) and 10% aqueous potassium carbonate (10 ml), the layers were separated, and the aqueous layer extracted with dichloromethane (3×20 ml). The combined dichloromethane extracts were dried (MgSO4) and concentrated in vacuo to leave a gum which was purified by column chromatography on silica eluting with dichloromethane containing methanol (0% up to 8%). The product-containing fractions were combined and concentrated in vacuo to leave an oil which was crystallised from diisopropyl ether to give the title compound as a colourless powder, yield 0.17 g, m.p. 131°-132° C.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 2 hours
  3. customThe mixture was partitioned between dichloromethane (50 ml) and 10% aqueous potassium carbonate (10 ml)
  4. customthe layers were separated
  5. extractionthe aqueous layer extracted with dichloromethane (3×20 ml)
  6. dry with materialThe combined dichloromethane extracts were dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customto leave a gum which
  9. customwas purified by column chromatography on silica eluting with dichloromethane
  10. additioncontaining methanol (0% up to 8%)
  11. concentrationconcentrated in vacuo
  12. customto leave an oil which
  13. customwas crystallised from diisopropyl ether

Sources & evidence

ORD record
ord-1dfa90cb4c24477ca55f0b554679926d
Source dataset
uspto-grants-1993_08
Patent number
US05233053

Reaction notes

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