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

HRID 2044960Notes

Reaction equation

HRID 2044960 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]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=1)[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:46]1(=[O:56])[NH:50][C:49](=[O:51])[C:48]2=[CH:52][CH:53]=[CH:54][CH:55]=[C:47]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]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=1)[C:6]([CH:12]([N:50]1[C:46](=[O:56])[C:47]3[C:48](=[CH:52][CH:53]=[CH:54][CH:55]=3)[C:49]1=[O:51])[CH3:13])=[N:7]2

Participants

6

Reactant 5

HCID 6809PhthalimideHCID 8028TetrahydrofuranHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 577079151-(5-Chloro-3-(3-fluorophenyl)quinoxalin-2-yl)ethanol

Product 1

HCID 577079112-(1-(5-Chloro-3-(3-fluorophenyl)quinoxalin-2-yl)ethyl)isoindoline-1,3-dione

Procedure

To a solution of 1-(5-chloro-3-(3-fluorophenyl)quinoxalin-2-yl)ethanol (0.2875 g, 0.9497 mmol) in tetrahydrofuran (9.497 mL, 0.9497 mmol) were added triphenyl-phosphine (0.7473 g, 2.849 mmol), phthalimide (0.4192 g, 2.849 mmol), and diisopropyl azodicarboxylate (0.5518 mL, 2.849 mmol). The reaction mixture was stirred at room temperature. After 1 h, the mixture was concentrated under reduced pressure and partitioned between EtOAc (100 mL) and brine (100 mL). The organic layer was 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 50% gradient of EtOAc in hexane over 20 min and 50% isocratic of EtOAc for 5 min as eluent to give 2-(1-(5-chloro-3-(3-fluorophenyl)quinoxalin-2-yl)ethyl)isoindoline-1,3-dione as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.19 (1 H, dd, J=8.4, 1.4 Hz), 8.09 (1 H, dd, J=7.6, 1.4 Hz), 7.91 (1 H, dd, J=8.4, 7.6 Hz), 7.73-7.80 (2 H, m), 7.60-7.68 (2 H, m), 7.31-7.38 (1 H, m), 7.14-7.24 (2 H, m), 7.00-7.09 (1 H, m), 6.04-6.13 (1 H, m), 1.77 (3 H, d, J=6.7 Hz); LC-MS (ESI) m/z 432.1 [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 organic layer was 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 20 min

Sources & evidence

ORD record
ord-f3d3b71d831848faa55adb97b740b64c
Source dataset
uspto-grants-2013_11
Patent number
US08586739B2

Reaction notes

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