Potassium Carbonate → Darifenacin Dehydro Impurity

HRID 2371874Notes

Reaction equation

HRID 2371874 reaction equation
[C:1]([C:4]([C@@H: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:33]=[CH:32][C:28]2[O:29][CH:30]=[CH:31][C:27]=2[CH:26]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[C:1]([C:4]([C@@H:17]1[CH2:21][CH2:20][N:19]([CH2:23][CH2:24][C:25]2[CH:33]=[CH:32][C:28]3[O:29][CH:30]=[CH:31][C:27]=3[CH:26]=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 13633758(S)-2,2-Diphenyl-2-(pyrrolidin-3-yl)acetamideHCID 19746812Benzofuran, 5-(2-bromoethyl)-

Product 1

HCID 22842830Darifenacin Dehydro Impurity

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture containing 3-(S)-(-)-(1-carbamoyl-1,1-diphenylmethyl)pyrrolidine (1.79 g--see Preparation 10(B)), 5-(2-bromoethyl)benzo[2,3-b]furan (1.2 g--see Preparation 17), anhydrous potassium carbonate (3 g) and acetonitrile (30 ml) was heated under reflux for 30 minutes. The mixture was partitioned between ethyl acetate (30 ml) and 10% aqueous potassium carbonate (30 ml), the layers were separated, and the aqueous layer extracted with ethyl acetate (3×50 ml). The combined ethyl acetate extracts were dried (MgSO4) and concentrated in vacuo to give a brown gum which was purified by column chromatography on silica eluting with dichloromethane containing methanol (2%). The product-containing fractions were combined and concentrated in vacuo to give the title compound as a foam, yield 1.4 g.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 30 minutes
  3. customThe mixture was partitioned between ethyl acetate (30 ml) and 10% aqueous potassium carbonate (30 ml)
  4. customthe layers were separated
  5. extractionthe aqueous layer extracted with ethyl acetate (3×50 ml)
  6. dry with materialThe combined ethyl acetate extracts were dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customto give a brown gum which
  9. customwas purified by column chromatography on silica eluting with dichloromethane
  10. additioncontaining methanol (2%)
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9801208849e341ffbaf221f79bcd0a38
Source dataset
uspto-grants-1992_03
Patent number
US05096890

Reaction notes

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