Acetone → HCID 57707929, compound

HRID 216870Notes

Reaction equation

HRID 216870 reaction equation
N[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([CH2:12][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])[C:8]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[Cl:30])=[N:7]2.CC(C)=O.Cl.N([O-])=O.[Na+].[I-:40].[K+]>>[Cl:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[C:8]1[C:9]([CH2:12][N:13]2[C:21](=[O:22])[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]2=[O:23])=[N:10][C:11]2[C:6]([N:7]=1)=[CH:5][CH:4]=[CH:3][C:2]=2[I:40]

Participants

6

Reactant 5

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 23668193Sodium NitriteHCID 57707974HCID 57707974, compound

Product 1

HCID 57707929HCID 57707929, compound

Conditions

Temperature
0 °C

Procedure

2-((8-amino-3-(2-chlorophenyl)quinoxalin-2-yl)methyl)isoindoline-1,3-dione (1.1337 g, 2.733 mmol) was dissolved in acetone (39.04 mL, 2.733 mmol) and cooled to 0° C. While being stirred, the solution was treated first with 2 M hydrochloric acid (7.652 mL, 15.30 mmol) and then dropwise with 1 M aq. sodium nitrite (5.466 mL, 5.466 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 (5.411 mL, 27.06 mmol) maintaining the temperature below 5° C. The mixture was then allowed to warm to 15° C. over 3.5 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×1) and saturated aqueous sodium bicarbonate (100 mL×1), brine (100 mL×1), dried over MgSO4, filtered, and concentrated under reduced pressure to give a dark violet syrupy solid. The dark violet syrupy 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 15 min and then 50% isocratic of EtOAc in hexane for 25 min as eluent to give 2-((3-(2-chlorophenyl)-8-iodoquinoxalin-2-yl)methyl)-isoindoline-1,3-dione as a solid: 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 3.5 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×1) 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 dark violet syrupy solid
  11. customThe dark violet syrupy solid was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column
  12. customover 15 min

Sources & evidence

ORD record
ord-79193a80355842d1a31c6cb052bb96ad
Source dataset
uspto-grants-2012_06
Patent number
US08193199B2

Reaction notes

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