Acetic Acid → 6-Bromo-1'-(methylsulfonyl)spiro[indoline-3,4'-piperidin]-2-one

HRID 1619107Notes

Reaction equation

HRID 1619107 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[Br:7][C:8]1[CH:16]=[C:15]2[C:11]([CH2:12][C:13](=[O:24])[N:14]2C(OC(C)(C)C)=O)=[CH:10][CH:9]=1.I[CH2:26][CH2:27][N:28]([CH2:33][CH2:34]I)[S:29]([CH3:32])(=[O:31])=[O:30].C(O)(=O)C>CN(C=O)C.O.C(OCC)(=O)C>[Br:7][C:8]1[CH:16]=[C:15]2[NH:14][C:13](=[O:24])[C:12]3([CH2:34][CH2:33][N:28]([S:29]([CH3:32])(=[O:31])=[O:30])[CH2:27][CH2:26]3)[C:11]2=[CH:10][CH:9]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 10796Cesium carbonateHCID 120261Methanesulfonamide, N,N-bis(2-iodoethyl)-HCID 58154275tert-Butyl 6-bromo-2-oxoindoline-1-carboxylate

Product 1

HCID 669587386-Bromo-1'-(methylsulfonyl)spiro[indoline-3,4'-piperidin]-2-oneYield 29%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Cesium carbonate (3.4 g, 10.6 mmol) was added portionwise over a 20 minute period to a stirred solution of tert-butyl 6-bromo-2-oxoindoline-1-carboxylate (preparation 8a, 1.0 g, 3.2 mmol) and N,N-bis(2-iodoethyl)methanesulfonamide (preparation 12b, 1.42 g, 3.5 mmol) in N,N′-dimethylformamide (50 mL) under an argon atmosphere. After the addition the mixture was warmed to room temperature and stirred overnight. Acetic acid (0.2 mL) followed by ethyl acetate and water were added to the reaction mixture and the organic layer was separated, washed with water, dried (MgSO4) and evaporated. The residue was treated with a 5M solution of hydrogen chloride in 1,4-dioxane (25 mL) and the mixture was stirred and heated to 70° C. After 30 minutes, the mixture was concentrated in vacuo and the residue was purified by flash chromatography (98:2 dichloromethane/methanol) to give the title compound (0.33 g, 29%) as a pale yellow solid.

Workup

  1. additionAfter the addition the mixture
  2. additionwere added to the reaction mixture
  3. customthe organic layer was separated
  4. washwashed with water
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. additionThe residue was treated with a 5M solution of hydrogen chloride in 1,4-dioxane (25 mL)
  8. stirringthe mixture was stirred
  9. temperatureheated to 70° C
  10. waitAfter 30 minutes
  11. concentrationthe mixture was concentrated in vacuo
  12. customthe residue was purified by flash chromatography (98:2 dichloromethane/methanol)

Sources & evidence

ORD record
ord-6ff4a779071b4064b45e4e2f98bb4738
Source dataset
uspto-grants-2014_07
Patent number
US08772288B2

Reaction notes

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