Triethylamine → 3-(4-Nitro-1-oxo-1,3-dihydroisoindol-2-yl)piperidine-2,6-dione

HRID 1843448Notes

Reaction equation

HRID 1843448 reaction equation
C(N(CC)CC)C.Cl.[NH2:9][CH:10]1[CH2:15][CH2:14][C:13](=[O:16])[NH:12][C:11]1=[O:17].Br[CH2:19][C:20]1[C:29]([N+:30]([O-:32])=[O:31])=[CH:28][CH:27]=[CH:26][C:21]=1[C:22](OC)=[O:23]>CN(C)C=O.C(#N)C>[O:23]=[C:22]1[C:21]2[C:20](=[C:29]([N+:30]([O-:32])=[O:31])[CH:28]=[CH:27][CH:26]=2)[CH2:19][N:9]1[CH:10]1[CH2:15][CH2:14][C:13](=[O:16])[NH:12][C:11]1=[O:17]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 1487795Methyl 2-(bromomethyl)-3-nitrobenzoate

Product 1

HCID 114717813-(4-Nitro-1-oxo-1,3-dihydroisoindol-2-yl)piperidine-2,6-dione

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
52.5 °C

Procedure

Triethylamine (140.8 g, 2.29 mol) was added at 25-30° C. to a solution of 3-amino-piperidine-2,6-dione hydrochloride (100 g, 0.61 mol) in N,N-dimethylformamide (800 ml). A solution of methyl 2-bromomethyl-3-nitro-benzoate (186.0 g, 1.13 mol) in acetonitrile (200 ml) was then added under stirring and a nitrogen atmosphere and the reaction mixture was heated to 50-55° C. for 8-10 hours. After completion of the reaction approximately 60% solvent was removed by distillation at 50-60° C. under reduced pressure (100 mbar). Water (1000 ml) was added to the residual mixture at 50-55° C. and stirred for 1 hour at this temperature. The resultant solid product was cooled to 25-30° C. and filtered. The solid was washed with water (500 ml) at 50-55° C., cooled at ambient temperature and filtered again. Finally the solid was washed with methanol (500 ml) at 50-55° C., cooled at 25-30° C. and filtered. The filtered solid product was dried at 50-55° C. under low pressure (200 mmHg) for 4 hours to give 3-(1-oxo-4-nitro-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione as a purple to ash coloured solid.

Workup

  1. customwas removed by distillation at 50-60° C. under reduced pressure (100 mbar)
  2. additionWater (1000 ml) was added to the residual mixture at 50-55° C.
  3. stirringstirred for 1 hour at this temperature
  4. temperatureThe resultant solid product was cooled to 25-30° C.
  5. filtrationfiltered
  6. washThe solid was washed with water (500 ml) at 50-55° C.
  7. temperaturecooled at ambient temperature
  8. filtrationfiltered again
  9. washFinally the solid was washed with methanol (500 ml) at 50-55° C.
  10. temperaturecooled at 25-30° C.
  11. filtrationfiltered
  12. customThe filtered solid product was dried at 50-55° C. under low pressure (200 mmHg) for 4 hours

Sources & evidence

ORD record
ord-6400b695636a438991ccf5baef9954ce
Source dataset
uspto-grants-2015_02
Patent number
US08946265B2

Reaction notes

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