Hydrochloric Acid → 2-Benzyl-7-methyl-2,3-dihydro-isoindol-1-one

HRID 2427641Notes

Reaction equation

HRID 2427641 reaction equation
[CH2:1]([N:8]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][C:14]=2[CH3:18])[C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Sn].Cl.C(OCC)(=O)C>C(O)(C)C.CCCCCC>[CH2:1]([N:8]1[CH2:9][C:10]2[C:15](=[C:14]([CH3:18])[CH:13]=[CH:12][CH:11]=2)[C:16]1=[O:17])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 5352426Tin atomHCID 579494822-Benzyl-4-methyl-isoindole-1,3-dione

Product 1

HCID 579493772-Benzyl-7-methyl-2,3-dihydro-isoindol-1-oneYield 9%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8058HexaneSolvent

Procedure

A mixture of 2-benzyl-4-methyl-isoindole-1,3-dione (0.500 g, 2 mmol), tin (0.59 g, 5 mmol) and concentrated HCl (2 mL) in isopropanol (10 mL) was heated at reflux for 2.5 h. After this time, the reaction mixture was cooled to ambient temperature, the solids removed by filtration and the filtrate concentrated. The resulting material was dissolved in dichloromethane (20 mL) and the solution washed with brine (7 mL). The organic solution was separated, dried over anhydrous MgSO4, filtered, and concentrated to afford a mixture of regio isomers. Silica gel column chromatography of this mixture using 25% ethyl acetate in hexane afforded 2-benzyl-7-methyl-2,3-dihydro-isoindol-1-one (0.02 g, 9%); 1H NMR (300 MHz, CDCl3): δ ppm) 2.68 (s, 3H), 4.23 (s, 2H), 4.77 (s, 2H), 7.15-7.40 (m, 8H) and GC-MS: m/z 237 (M)+, 160 (M−77)+; and 2-benzyl-4-methyl-2,3-dihydro-isoindol-1-one (0.02 g, 9%); 1H NMR (300 MHz, CDCl3): δ (ppm) 2.68 (s, 3H), 4.23 (s, 2H), 4.77 (s, 2H), 7.15-7.40 (m, 8H) and GC-MS: m/z 237 (M)+, 160 (M−77)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2.5 h
  3. customthe solids removed by filtration
  4. concentrationthe filtrate concentrated
  5. dissolutionThe resulting material was dissolved in dichloromethane (20 mL)
  6. washthe solution washed with brine (7 mL)
  7. customThe organic solution was separated
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford
  12. additiona mixture of regio isomers

Sources & evidence

ORD record
ord-90aff08142e54a59aa64bd3a87088dec
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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