Hydrogen Bromide → Darifenacin

HRID 2118060Notes

Reaction equation

HRID 2118060 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][CH2:11][N:12]3[CH2:16][CH2:15][CH:14]([C:17]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[C:18]([NH2:20])=[O:19])[CH2:13]3)=[CH:9][C:4]=2[CH:3]=[CH:2]1.C(O)CCC.Br>C(O)(=O)C.[Pd]>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][CH2:11][N:12]3[CH2:16][CH2:15][C@@H:14]([C:17]([C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[C:18]([NH2:20])=[O:19])[CH2:13]3)=[CH:9][C:4]=2[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 260Hydrogen BromideHCID 2631-ButanolHCID 197468032-{1-[2-(Benzofuran-5-yl)ethyl]-3-pyrrolidinyl}-2,2-diphenylacetamide

Product 1

HCID 444031DarifenacinYield 85%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent

Procedure

Pd/C 10% (0.8 g) was added to a solution of S)-2-{1-[2-(benzofuran-5-yl)ethyl]-3-pyrrolidinyl}-2,2-diphenylacetamide (8 g) in acetic acid (160 ml). The mixture was hydrogenated at 45-50° C. and at atmospheric pressure for about 6-7 hrs. Catalyst was filtered off and solution was concentrated under vacuum obtaining an oily residue. n-Butanol (40 ml) was added and stirred to obtain a solution. 48% HBr (3.5 g) was added and a mixture n-Butanol/water was eliminated by distillation to reduce water content to less then 1%. Darifenacin .HBr crystallizes and after 2 hrs at 15-20° C. was filtered and washed with n-Butanol (3×5 ml). After drying at 55-60° C. under vacuum 8.1 g of Darifenacin hydrobromide were obtained. (Yield 85%).

Workup

  1. filtrationCatalyst was filtered off
  2. concentrationsolution was concentrated under vacuum
  3. customobtaining an oily residue
  4. customto obtain a solution
  5. distillationa mixture n-Butanol/water was eliminated by distillation
  6. customHBr crystallizes and after 2 hrs at 15-20° C.
  7. filtrationwas filtered
  8. washwashed with n-Butanol (3×5 ml)
  9. dry with materialAfter drying at 55-60° C. under vacuum 8.1 g of Darifenacin hydrobromide
  10. customwere obtained

Sources & evidence

ORD record
ord-c42a57a650104b7e8b1a47eb557fc1ea
Source dataset
uspto-grants-2008_10
Patent number
US07442806B2

Reaction notes

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