Acetic Acid → 2-(4-(Methylthio)benzyl)isoindoline-1,3-dione

HRID 527340Notes

Reaction equation

HRID 527340 reaction equation
[CH3:1][S:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][NH2:8])=[CH:5][CH:4]=1.[C:11]1(=O)[O:16][C:14](=[O:15])[C:13]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:12]12.C(O)(=O)C>>[CH3:1][S:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][N:8]2[C:14](=[O:15])[C:13]3[C:12](=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:11]2=[O:16])=[CH:5][CH:4]=1

Participants

4

Reactant 3

HCID 176Acetic AcidHCID 6811Phthalic AnhydrideHCID 27600804-(Methylthio)benzylamine

Product 1

HCID 79600652-(4-(Methylthio)benzyl)isoindoline-1,3-dione

Procedure

A mixture of 4-(methylthio)benzylamine (2.00 mL, 2.20 g, 14.38 mmol) and phthalic anhydride (2.39 g, 15.79 mmol) in acetic acid (40 mL, 42 g, 700 mmol) is heated at reflux for 3 h. The mixture is concentrated under reduced pressure, and the residue is partitioned between water and dichloromethane. The phases are separated, and the aqueous phase is extracted twice with dichloromethane. The combined organic layers are concentrated under reduced pressure and the residue is purified by flash chromatography on silica (gradient cyclohexane/ethyl acetate 9:1 to 7:3). Yield: 3.60 g (88% of theory); ESI mass spectrum: [M+H]+=284; r.t. HPLC: 0.75 min (X001_004).

Workup

  1. temperatureis heated
  2. temperatureat reflux for 3 h
  3. concentrationThe mixture is concentrated under reduced pressure
  4. customthe residue is partitioned between water and dichloromethane
  5. customThe phases are separated
  6. extractionthe aqueous phase is extracted twice with dichloromethane
  7. concentrationThe combined organic layers are concentrated under reduced pressure
  8. customthe residue is purified by flash chromatography on silica (gradient cyclohexane/ethyl acetate 9:1 to 7:3)
  9. customr.t
  10. custom0.75 min (X001_004)

Sources & evidence

ORD record
ord-350428f477dc48329b2134a3d41d0745
Source dataset
uspto-grants-2016_05
Patent number
US09346794B1

Reaction notes

Loading…