Phthalimide → 2-(1-(5-Chloro-3-(2-chloro-5-fluorophenyl)quinoxalin-2-yl)ethyl)isoindoline-1,3-dione

HRID 216877Notes

Reaction equation

HRID 216877 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[N:4]=[C:5]([C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[Cl:22])[C:6]([CH:12](O)[CH3:13])=[N:7]2.O1CCCC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:47]1(=[O:57])[NH:51][C:50](=[O:52])[C:49]2=[CH:53][CH:54]=[CH:55][CH:56]=[C:48]12.N(C(OC(C)C)=O)=NC(OC(C)C)=O>>[Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[N:4]=[C:5]([C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[Cl:22])[C:6]([CH:12]([N:51]1[C:47](=[O:57])[C:48]3[C:49](=[CH:53][CH:54]=[CH:55][CH:56]=3)[C:50]1=[O:52])[CH3:13])=[N:7]2

Participants

6

Reactant 5

HCID 6809PhthalimideHCID 8028TetrahydrofuranHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 577079211-(5-Chloro-3-(2-chloro-5-fluorophenyl)quinoxalin-2-yl)ethanol

Product 1

HCID 577079262-(1-(5-Chloro-3-(2-chloro-5-fluorophenyl)quinoxalin-2-yl)ethyl)isoindoline-1,3-dione

Procedure

To a solution of 1-(5-chloro-3-(2-chloro-5-fluorophenyl)quinoxalin-2-yl)ethanol (0.08320 g, 0.2468 mmol) in tetrahydrofuran (2.468 mL, 0.2468 mmol) were added triphenylphosphine (0.07766 g, 0.2961 mmol), phthalimide (0.04357 g, 0.2961 mmol), and diisopropyl azodicarboxylate (0.05735 mL, 0.2961 mmol). The reaction mixture was stirred at room temperature. After 6 h, the mixture was concentrated under reduced pressure and partitioned between EtOAc (100 mL) and brine (100 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography on a 40 g of Redi-Sep™ column using 0 to 10% gradient of EtOAc in hexane over 10 min, then 10% isocratic of EtOAc for 20 min, then 10 to 50% gradient of EtOAc in hexane over 20 min, then 50% isocratic of EtOAc for 3 min as eluent to give 2-(1-(5-chloro-3-(2-chloro-5-fluorophenyl)quinoxalin-2-yl)ethyl)isoindoline-1,3-dione as a tan solid: LC-MS (ESI) m/z 466.0 [M+H]+.

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. custompartitioned between EtOAc (100 mL) and brine (100 mL)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography on a 40 g of Redi-Sep™ column
  7. customover 10 min
  8. wait10% isocratic of EtOAc for 20 min
  9. wait10 to 50% gradient of EtOAc in hexane over 20 min

Sources & evidence

ORD record
ord-bd6457b5b494414da5519fed36a7f761
Source dataset
uspto-grants-2012_06
Patent number
US08193199B2

Reaction notes

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