Acetone → Phthalimide

HRID 1397783Notes

Reaction equation

HRID 1397783 reaction equation
NC1C=CC=C2C=1N=C(C1C=CC=CC=1Cl)C(C[N:13]1[C:21](=[O:22])[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]1=[O:23])=N2.CC(C)=O.Cl.N([O-])=O.[Na+].[I-].[K+]>>[C:14]1(=[O:23])[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:21](=[O:22])[NH:13]1

Participants

6

Reactant 5

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 23668193Sodium NitriteHCID 57707936HCID 57707936, compound

Product 1

HCID 6809Phthalimide

Conditions

Temperature
0 °C

Procedure

2-((5-amino-3-(2-chlorophenyl)quinoxalin-2-yl)methyl)isoindoline-1,3-dione (Prepared in Example 97, 0.8364 g, 2.016 mmol) was dissolved in acetone (28.80 mL, 2.016 mmol) and cooled to 0° C. While being stirred, the solution was treated first with 2 M hydrochloric acid (5.645 mL, 11.29 mmol) and then dropwise with 1 M aq. sodium nitrite (6.049 mL, 6.049 mmol) while maintaining the temperature of the mixture at 0° C. After the additions were complete, the mixture was stirred for 15 min and then treated with 5 M aq. potassium iodide (4.839 mL, 24.19 mmol) maintaining the temperature below 5° C. The mixture was then allowed to warm to 15° C. over 3 h. The acetone was removed under reduced pressure, and the residue was partitioned between water (100 mL) and ethyl acetate (100 mL). The organic solution was washed with 10% aqueous sodium bisulfite (100 mL×3) and saturated aqueous sodium bicarbonate (100 mL×1), brine (100 mL×1), dried over MgSO4, filtered, and concentrated under reduced pressure to give a red solid. The red solid was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column using 0 to 50% gradient of EtOAc in hexane over 25 min and then 50% isocratic of EtOAc in hexane for 25 min as eluent to give 24(3-(2-chlorophenyl)-5-iodoquinoxalin-2-yl)methyl)-isoindoline-1,3-dione as a solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.48 (1 H, dd, J=7.4, 1.2 Hz), 7.97 (1 H, dd, J=8.2, 1.2 Hz), 7.83-7.91 (4 H, m), 7.51-7.75 (5 H, m), 4.96 (2 H, d, J=21.9 Hz); LC-MS (ESI) m/z 526.0 [M+H]+.

Workup

  1. stirringthe mixture was stirred for 15 min
  2. temperaturemaintaining the temperature below 5° C
  3. temperatureto warm to 15° C. over 3 h
  4. customThe acetone was removed under reduced pressure
  5. customthe residue was partitioned between water (100 mL) and ethyl acetate (100 mL)
  6. washThe organic solution was washed with 10% aqueous sodium bisulfite (100 mL×3) and saturated aqueous sodium bicarbonate (100 mL×1), brine (100 mL×1)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto give a red solid
  11. customThe red solid was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column
  12. customover 25 min

Sources & evidence

ORD record
ord-d77eae6afad94467a00a948db44e410b
Source dataset
uspto-grants-2014_12
Patent number
US08901135B2

Reaction notes

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