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

HRID 661522Notes

Reaction equation

HRID 661522 reaction equation
[OH-].[K+].[C:3]([O:7][C:8]([N:10]1[CH2:14][CH2:13][C:12]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)([C:15]([C:17]2[CH:18]=[C:19]3[C:23](=[CH:24][CH:25]=2)[NH:22][CH:21]=[CH:20]3)=[O:16])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[I:33]I.[H-].[Na+].[C:37]1([S:43](Cl)(=[O:45])=[O:44])[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>CN(C=O)C>[C:3]([O:7][C:8]([N:10]1[CH2:14][CH2:13][C:12]([C:15]([C:17]2[CH:18]=[C:19]3[C:23](=[CH:24][CH:25]=2)[N:22]([S:43]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)(=[O:45])=[O:44])[CH:21]=[C:20]3[I:33])=[O:16])([CH2:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

7

Reactant 5

HCID 807IodineHCID 7369Benzenesulfonyl chlorideHCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 666872373-benzyl-3-(1H-indole-5-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 666872663-(1-benzenesulfonyl-3-iodo-1H-indole-5-carbonyl)-3-benzyl-pyrrolidine-1-carboxylic acid tert-butyl esterYield 91%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Freshly crushed potassium hydroxide (35 mg, 0.617 mmol) was added to a solution of 3-benzyl-3-(1H-indole-5-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (100 mg, 0.247 mmol) in DMF (1.5 mL). A solution of iodine (63 mg, 0.247 mmol) in DMF (0.5 mL) was then added dropwise, and the reaction mixture was stirred at room temperature for 45 minutes. The reaction was quenched by addition of an aqueous solution of Na2S2O3 and diluted with water. The resulting mixture was extracted with EtOAc; the combined organic extracts were washed with water, dried over MgSO4, filtered and evaporated under reduced pressure. The residue was immediately dissolved in DMF (2 mL), and NaH (60% in mineral oil, 12 mg, 0.296 mmol) was added to the solution. The resulting mixture was stirred for 20 minutes, after which benzenesulfonyl chloride (38 μL, 0.296 mmol) was then added dropwise. The reaction mixture was stirred for 30 minutes, then quenched by addition of water. The resulting mixture was extracted with EtOAc, and the combined organic extracts were washed with water, dried over MgSO4, filtered and evaporated under reduced pressure. The residue was purified by flash chromatography (10% to 30% of EtOAc in hexane) to give 150 mg (91% yield) of 3-(1-benzenesulfonyl-3-iodo-1H-indole-5-carbonyl)-3-benzyl-pyrrolidine-1-carboxylic acid tert-butyl ester as a white foam.

Workup

  1. customThe reaction was quenched by addition of an aqueous solution of Na2S2O3
  2. additiondiluted with water
  3. extractionThe resulting mixture was extracted with EtOAc
  4. washthe combined organic extracts were washed with water
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. dissolutionThe residue was immediately dissolved in DMF (2 mL)
  9. stirringThe resulting mixture was stirred for 20 minutes
  10. stirringThe reaction mixture was stirred for 30 minutes
  11. customquenched by addition of water
  12. extractionThe resulting mixture was extracted with EtOAc
  13. washthe combined organic extracts were washed with water
  14. dry with materialdried over MgSO4
  15. filtrationfiltered
  16. customevaporated under reduced pressure
  17. customThe residue was purified by flash chromatography (10% to 30% of EtOAc in hexane)

Sources & evidence

ORD record
ord-cabfa294e7ac4af9a30eed0e17869363
Source dataset
uspto-grants-2011_12
Patent number
US08084623B2

Reaction notes

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