3-(1-benzenesulfonyl-3-iodo-1H-indole-5-carbonyl)-3-benzyl-pyrrolidine-1-carboxylic acid tert-butyl ester → 3-(1-benzenesulfonyl-3-cyano-1H-indole-5-carbonyl)-3-benzyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 661523Notes

Reaction equation

HRID 661523 reaction equation
[Cu][C:2]#[N:3].[C:4]([O:8][C:9]([N:11]1[CH2:15][CH2:14][C:13]([C:23]([C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][CH:33]=2)[N:30]([S:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)(=[O:36])=[O:35])[CH:29]=[C:28]3I)=[O:24])([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:12]1)=[O:10])([CH3:7])([CH3:6])[CH3:5]>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.O1CCOCC1>[C:4]([O:8][C:9]([N:11]1[CH2:15][CH2:14][C:13]([C:23]([C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][CH:33]=2)[N:30]([S:34]([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)(=[O:36])=[O:35])[CH:29]=[C:28]3[C:2]#[N:3])=[O:24])([CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:12]1)=[O:10])([CH3:7])([CH3:5])[CH3:6]

Participants

6

Reactant 2

HCID 666872663-(1-benzenesulfonyl-3-iodo-1H-indole-5-carbonyl)-3-benzyl-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 178418546HCID 178418546, compound

Product 1

HCID 666874943-(1-benzenesulfonyl-3-cyano-1H-indole-5-carbonyl)-3-benzyl-pyrrolidine-1-carboxylic acid tert-butyl esterYield 95%

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

Copper(I) cyanide (76 mg, 0.852 mmol) was added to a 25 mL round bottom flask charged with 3-(1-benzenesulfonyl-3-iodo-1H-indole-5-carbonyl)-3-benzyl-pyrrolidine-1-carboxylic acid tert-butyl ester (143 mg, 0.213 mmol), followed by 1,1′-bis(diphenylphosphino)ferrocene (24 mg, 0.043 mmol) and tris(dibenzylideneacetone) dipalladium(0) (10 mg, 0.011 mmol). 1,4-Dioxane (1.5 mL) was then added and the mixture was heated to reflux under nitrogen atmosphere for one hour. The reaction mixture was cooled to room temperature and filtered through a celite pad. The filter cake was rinsed with EtOAc and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (30% of EtOAc in hexane) to give 115 mg (95% yield) of 3-(1-benzenesulfonyl-3-cyano-1H-indole-5-carbonyl)-3-benzyl-pyrrolidine-1-carboxylic acid tert-butyl ester as a pale yellow foam.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux under nitrogen atmosphere for one hour
  3. filtrationfiltered through a celite pad
  4. washThe filter cake was rinsed with EtOAc
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by flash chromatography (30% of EtOAc in hexane)

Sources & evidence

ORD record
ord-68af7d006b1b428bb00517b280112a27
Source dataset
uspto-grants-2011_12
Patent number
US08084623B2

Reaction notes

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