Water → 2-(1-(3,5-Dichloroquinoxalin-2-yl)ethyl)isoindoline-1,3-dione

HRID 75374Notes

Reaction equation

HRID 75374 reaction equation
Br[CH:2]([C:4]1[C:13]([Cl:14])=[N:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[Cl:15])[N:5]=1)[CH3:3].[C:16]1(=[O:26])[NH:20][C:19](=[O:21])[C:18]2=[CH:22][CH:23]=[CH:24][CH:25]=[C:17]12.[K].O.CCOC(C)=O>CN(C=O)C>[Cl:14][C:13]1[C:4]([CH:2]([N:20]2[C:16](=[O:26])[C:17]3[C:18](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:19]2=[O:21])[CH3:3])=[N:5][C:6]2[C:11]([N:12]=1)=[C:10]([Cl:15])[CH:9]=[CH:8][CH:7]=2

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 24194345Phthalimide potassium saltHCID 866985112-(1-Bromoethyl)-3,5-dichloroquinoxaline

Product 1

HCID 866985122-(1-(3,5-Dichloroquinoxalin-2-yl)ethyl)isoindoline-1,3-dioneYield 101.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(1-bromoethyl)-3,5-dichloroquinoxaline (1.00 Kg, 3.27 mol) in DMF (8.2 L) was added potassium phthalimide (1.21 Kg, 6.54 mol). The reaction mixture was stirred for 3 h. At this time LC-MS analysis showed that the reaction was complete. The mixture was transferred to a 50 L separatory funnel and water (12 L) and EtOAc (6 L) were added to it with stirring. A large amount of white solid crashed out and was collected by filtration. The aqueous. phase was separated and extracted again with EtOAc (2×4 L). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and the volume was reduced to 5 L under reduced pressure. After cooling to rt, the product was obtained as a white solid. The white solid was filtered, triturated with hexane and dried under vacuum to give 2-(1-(3,5-dichloroquinoxalin-2-yl)ethyl)isoindoline-1,3-dione (1.24 Kg). 1H NMR (DMSO-d6) δ ppm 8.02-8.21 (2H, m), 7.83-8.02 (m, 5H), 5.89 (q, J=6.8 Hz, 1H), 1.87 (d, J=6.8 Hz, 3H). Mass Spectrum (ESI) m/z=372.0 (M+1).

Workup

  1. customThe mixture was transferred to a 50 L separatory funnel
  2. stirringwith stirring
  3. filtrationwas collected by filtration
  4. customphase was separated
  5. extractionextracted again with EtOAc (2×4 L)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. customthe product was obtained as a white solid
  10. filtrationThe white solid was filtered
  11. customtriturated with hexane
  12. customdried under vacuum

Sources & evidence

ORD record
ord-ebc37859c39c4cfb984781b31f2aef87
Source dataset
uspto-grants-2014_09
Patent number
US08835432B2

Reaction notes

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