(R)-5-(2-Ethylsulphonylethenyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole → (R)-5-(2-Ethylsulphonylethyl)-3-(N-methylpyrrolidin-2-ylmethyl)1H-indole

HRID 1901569Notes

Reaction equation

HRID 1901569 reaction equation
[CH2:1]([S:3]([CH:6]=[CH:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[C:11]2[CH2:17][C@H:18]1[CH2:22][CH2:21][CH2:20][N:19]1[CH3:23])(=[O:5])=[O:4])[CH3:2]>Cl.CN(C)C=O.O.[Pd]>[CH2:1]([S:3]([CH2:6][CH2:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[C:11]2[CH2:17][C@H:18]1[CH2:22][CH2:21][CH2:20][N:19]1[CH3:23])(=[O:5])=[O:4])[CH3:2]

Participants

6

Reactant 1

HCID 54504320(R)-5-(2-Ethylsulphonylethenyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole

Product 1

HCID 9884122(R)-5-(2-Ethylsulphonylethyl)-3-(N-methylpyrrolidin-2-ylmethyl)1H-indoleYield 69.6%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(R)-5-(2-Ethylsulphonylethenyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole (157 mg) was dissolved in a mixture of ethanolic hydrogen chloride [prepared by addition of acetyl chloride (0.043 mL) to ethanol (10 mL)], N,N-dimethylformamide (7.5 mL) and water (0.1 mL) and the solution was shaken under a hydrogen atmosphere (15 psi) at room temperature for 18 hours in the presence of 10% palladium on carbon (150 mg). The mixture was filtered through Arbacel (trade mark) filter aid and the residue was washed well with ethanol. The combined filtrate and washings were evaporated under reduced pressure and the residual oil was partitioned between ethyl acetate and 2M aqueous sodium carbonate solution. The organic layer was separated, washed three times with water followed by brine and then dried (Na2SO4). Evaporation of the solvent gave an oil which was chromatographed on silica gel. Elution with dichloromethane/methanol/concentrated aqueous ammonia (90:10:1) gave the title compound as a gum (110 mg): TLC (CH2Cl2 /C2H5OH/NH3 ; 90:10:1): Rf =0.3; [α]25D =+62° (methanol, c=0.10). Anal. Calcd for C18H26N2O2S. 0.05 CH2Cl2 : C,63.21; H,7.67; N,8.17. Found: C,63.55; H,7.61; N,8.41.

Workup

  1. filtrationThe mixture was filtered through Arbacel (trade mark)
  2. filtrationfilter aid
  3. washthe residue was washed well with ethanol
  4. customThe combined filtrate and washings were evaporated under reduced pressure
  5. customthe residual oil was partitioned between ethyl acetate and 2M aqueous sodium carbonate solution
  6. customThe organic layer was separated
  7. washwashed three times with water
  8. dry with materialdried (Na2SO4)
  9. customEvaporation of the solvent
  10. customgave an oil which
  11. customwas chromatographed on silica gel
  12. washElution with dichloromethane/methanol/concentrated aqueous ammonia (90:10:1)

Sources & evidence

ORD record
ord-9e4fda96174a4a9a9b1602557e31c813
Source dataset
uspto-grants-1996_11
Patent number
US05578612

Reaction notes

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