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

HRID 1016535Notes

Reaction equation

HRID 1016535 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/C18 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-048c240c0da74c94b70cb1402005b285
Source dataset
uspto-grants-2002_11
Patent number
US06476052B1

Reaction notes

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