Dimethylformamide → 3-Oxoisoindoline-5-carbonitrile

HRID 410487Notes

Reaction equation

HRID 410487 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][NH:7][C:8]2=[O:11])=[CH:4][CH:3]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH3:31][N:32](C=O)C>CC([O-])=O.CC([O-])=O.[Pd+2].[C-]#N.[C-]#N.[Zn+2]>[O:11]=[C:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([C:31]#[N:32])[CH:10]=2)[CH2:6][NH:7]1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 11776TriphenylphosphineHCID 222209196-Bromo-2,3-dihydro-1H-isoindol-1-one

Product 1

HCID 197881093-Oxoisoindoline-5-carbonitrileYield 78%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
100 °C

Procedure

A mixture of 6-bromo-2,3-dihydro-1H-isoindol-1-one (150 g, 0.71 mol), Pd(OAc)2 (7.92 g, 0.036 mol), PPh3 (27.9 g, 0.106 mol), Zn(CN)2 (124.6 g, 1.065 mol) and 500 ml of DMF was stirred at 100° C. overnight. Cooled to rt, the solvent was removed and the residue was dissolved in EtOAc. The solid was removed and the filtrate was washed with brine, dried over Na2SO4, evaporated to afford the crude product, which was purified by flash column chromatography on silica gel to afford 3-oxo-2,3-dihydro-1H-isoindole-5-carbonitrile (87.5 g, 78% yield).

Workup

  1. temperatureCooled to rt
  2. customthe solvent was removed
  3. dissolutionthe residue was dissolved in EtOAc
  4. customThe solid was removed
  5. washthe filtrate was washed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customto afford the crude product, which
  9. customwas purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-f55ac1a84d04468aae8cd7b9fb95852c
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

Loading…