Dimethylformamide → 1-(2-Diethylaminoethyl)-3-hydroxy-3-(2-chlorophenyl)-4-bromo-6-cyanooxindole

HRID 1369097Notes

Reaction equation

HRID 1369097 reaction equation
C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH2:20]([N:22]([CH2:45][CH3:46])[CH2:23][CH2:24][N:25]1[C:33]2[C:28](=[C:29]([Br:35])[CH:30]=[C:31](I)[CH:32]=2)[C:27]([OH:43])([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[Cl:42])[C:26]1=[O:44])[CH3:21].[CH3:47][N:48](C=O)C>CCOC(C)=O.C1(C)C=CC=CC=1.[C-]#N.[C-]#N.[Zn+2]>[CH2:20]([N:22]([CH2:45][CH3:46])[CH2:23][CH2:24][N:25]1[C:33]2[C:28](=[C:29]([Br:35])[CH:30]=[C:31]([C:47]#[N:48])[CH:32]=2)[C:27]([OH:43])([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[Cl:42])[C:26]1=[O:44])[CH3:21]

Participants

6

Reactant 3

HCID 6228Dimethylformamide2×HCID 11776TriphenylphosphineHCID 185186541-(2-Diethylaminoethyl)-3-hydroxy-3-(2-chlorophenyl)-4-bromo-6-iodooxindole

Product 1

HCID 185185971-(2-Diethylaminoethyl)-3-hydroxy-3-(2-chlorophenyl)-4-bromo-6-cyanooxindoleYield 91%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 21584019Toluene ethylacetateSolvent

Procedure

To Pd2(dba)3CHCl3 (60.1 mg, 5 mol %) and PPh3 (60.9 mg, 20 mol %) under a nitrogen atmosphere was added anhydrous DMF (0.5 mL). The resulting precipitate was stirred at room temperature for 30 minutes during which time the colour changed from red to yellow/orange. To this was added 1-(2-diethylaminoethyl)-3-hydroxy-3-(2-chlorophenyl)-4-bromo-6-iodooxindole (626.4 mg, 1.16 mmol) dissolved in anhydrous DMF (1.0 mL). To the resulting red solution was then added Zn(CN)2. The resulting precipitate was then heated to 60° C. (bath temperature) and stirring was continued at that temperature for 4 hours. The mixture was allowed to cool to room temperature and diluted with EtOAc:toluene (1:1, 10 mL). The mixture was washed with H2O (6 mL). The aqueous phase was then extracted with EtOAc:toluene (1:1, 5 mL×5). The organic phases were combined and dried (anhydrous MgSO4). After filtration the solvent was removed in vacuo. The orange solid obtained was then purified by flash chromatography (silica gel, eluting 1% to 2% to 3%MeOH in CHCl3) to give the title compound as a light brown/orange solid (462.6 mg, 91%).

Workup

  1. temperatureThe resulting precipitate was then heated to 60° C. (bath temperature)
  2. stirringstirring
  3. waitwas continued at that temperature for 4 hours
  4. temperatureto cool to room temperature
  5. washThe mixture was washed with H2O (6 mL)
  6. extractionThe aqueous phase was then extracted with EtOAc:toluene (1:1, 5 mL×5)
  7. dry with materialdried (anhydrous MgSO4)
  8. filtrationAfter filtration the solvent
  9. customwas removed in vacuo
  10. customThe orange solid obtained
  11. customwas then purified by flash chromatography (silica gel, eluting 1% to 2% to 3%MeOH in CHCl3)

Sources & evidence

ORD record
ord-0771f6c9e78a448aa688403e8d64dc07
Source dataset
uspto-grants-2003_06
Patent number
US06576656B1

Reaction notes

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