Allyl bromide → N-Allyloxyphthalimide

HRID 1663128Notes

Reaction equation

HRID 1663128 reaction equation
[OH:1][N:2]1[C:6](=[O:7])[C:5]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:4]2[C:3]1=[O:12].C(N(CC)CC)C.[CH2:20](Br)[CH:21]=[CH2:22]>CN(C=O)C>[CH2:22]([O:1][N:2]1[C:3](=[O:12])[C:4]2[C:5](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]1=[O:7])[CH:21]=[CH2:20]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 8471TriethylamineHCID 10665N-Hydroxyphthalimide

Product 1

HCID 2765097N-Allyloxyphthalimide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-Hydroxyphthalimide (48.9 g) was dissolved in DMF (200 ml) and triethylamine (43.9 ml) was added followed by addition of allyl bromide. The reaction mixture was stirred at room temperature for 18 hours and the resulting precipitated material was removed by filtration. The filtrate was concentrated under reduced pressure. The residue was dissolved in dichloromethane and washed with saturated aqueous sodium bicarbonate, 4 M HCl aq. and brine. The organic layer was dried (MgSO4) and evaporated under reduced pressure. The remaining material was crystallised from hexane/EtOAc, affording 2-allyloxy-isoindole-1,3-dione (43.6 g). This allyl intermediate (2.03 g) was dissolved in toluene (5 ml) and nitroethane (825 mg), phenylisocyanate (2.4 ml) and triethylamine (0.02 eq.) was added. The reaction mixture was stirred at room temperature for 48 hours, and the precipitated material was removed by filtration. The filtrate was evaporated onto silica gel and chromatographed (0 to 50% EtOAc/heptane) and gave 2-(3-methyl-4,5-dihydro-isoxazol-5-ylmethoxy)-isoindole-1,3-dione (2.4 g). 13C-NMR (DMSO-d6) δ 162.9, 155.4, 134.7, 128.5, 123.2, 78.0, 76.9, 40.3, 12.4. This phthalimide intermediate (260 mg) was dissolved in methanol (1 ml) and dichloromethane (1 ml) and hydrazine monohydrate (1.0 eq.) was added. The mixture was stirred at room temperature for 20 hours. The formed solid material was removed by filtration. The filtrate was evaporated under reduced pressure and gave the title compound, which was used without further purification.

Workup

  1. customthe resulting precipitated material
  2. customwas removed by filtration
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in dichloromethane
  5. washwashed with saturated aqueous sodium bicarbonate, 4 M HCl aq. and brine
  6. dry with materialThe organic layer was dried (MgSO4)
  7. customevaporated under reduced pressure
  8. customThe remaining material was crystallised from hexane/EtOAc

Sources & evidence

ORD record
ord-a75fdf9e6afe47a4b38bf401e7434df3
Source dataset
uspto-grants-2011_10
Patent number
US08034811B2

Reaction notes

Loading…