3-(3-Nitrophthalimido)-3-methylpiperidine-2,6-dione → 4-Amino-2-(3-methyl-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione

HRID 651439Notes

Reaction equation

HRID 651439 reaction equation
[N+:1]([C:4]1[CH:23]=[CH:22][CH:21]=[C:6]2[C:7]([N:9]([C:12]3([CH3:20])[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]3=[O:19])[C:10](=[O:11])[C:5]=12)=[O:8])([O-])=O.[H][H]>CC(C)=O.C(OCC)(=O)C.[Pd]>[NH2:1][C:4]1[CH:23]=[CH:22][CH:21]=[C:6]2[C:7]([N:9]([C:12]3([CH3:20])[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]3=[O:19])[C:10](=[O:11])[C:5]=12)=[O:8]

Participants

6

Reactant 2

HCID 155520373-(3-Nitrophthalimido)-3-methylpiperidine-2,6-dioneHCID 178418361HCID 178418361, compound

Product 1

HCID 115220774-Amino-2-(3-methyl-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dioneYield 82%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-(3-Nitrophthalimido)-3-methylpiperidine-2,6-dione (0.5 g, 1.57 mmol) was dissolved in acetone (250 mL) with gentle heat and then cooled to room temperature. To this solution was added 10% Pd/C (0.1 g) under nitrogen. The mixture was hydrogenated in a Parr apparatus at 50 psi of hydrogen for 4 hours. The mixture then was filtered through Celite and the pad washed with acetone (50 mL). The filtrate was concentrated in vacuo to yield a yellow solid. The solid was slurried in ethyl acetate (10 mL) for 30 minutes. The slurry then was filtered and dried (60° C., <1 mm) to afford 0.37 g (82%) of 3-(3-aminophthalimido)-3-methylpiperidine-2,6-dione as a yellow solid: mp 268-269° C.; 1H NMR (DMSO-d6) δ10.98 (s. 1H), 7.44 (dd, J=7.1 and 7.3 Hz, 1H), 6.99 (d, J=8.4 Hz, 1H), 6.94 (d, J=6.9 Hz, 1H), 6.52 (s, 2H), 2.71-2.47 (m, 3H), 2.08-1.99 (m. 1H), 1.87 (s, 3H); 13C NMR (DMSO-d6) δ172.48, 172.18, 169.51, 168.06, 146.55, 135.38, 131.80, 121.51, 110.56, 108.30, 58.29, 29.25, 28.63, 21.00; HPLC, Water Nova-Pak/Cl8 column, 4 micron, 1 mL/min, 240 nm, 20/80 CH3CN/0.1% H3PO4(aq), 5.62 min (99.18%). Anal. Calcd For C14H13N3O4: C, 58.53; H, 4.56; N, 14.63. Found: C, 58.60; H, 4.41; N, 14.36.

Workup

  1. temperaturewith gentle heat
  2. filtrationThe mixture then was filtered through Celite
  3. washthe pad washed with acetone (50 mL)
  4. concentrationThe filtrate was concentrated in vacuo
  5. customto yield a yellow solid
  6. filtrationThe slurry then was filtered
  7. customdried (60° C., <1 mm)

Sources & evidence

ORD record
ord-0d54d1c16ffb4480b9aac26401bb5f9c
Source dataset
uspto-grants-2001_08
Patent number
US06281230B1

Reaction notes

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