3-Aminopiperidine-2,6-dione hydrochloride → 2-(2,6-Dioxo-piperidin-3-yl)-4-(3-methyl-benzyloxy)-isoindole-1,3-dione

HRID 709560

Reaction equation

HRID 709560 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[CH2:5][O:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:9]([C:10]([OH:12])=O)[C:8]=1[C:16]([OH:18])=O.Cl.[NH2:23][CH:24]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:25]1=[O:26]>N1C=CC=CC=1>[O:26]=[C:25]1[CH:24]([N:23]2[C:16](=[O:18])[C:8]3[C:9](=[CH:13][CH:14]=[CH:15][C:7]=3[O:6][CH2:5][C:4]3[CH:19]=[CH:20][CH:21]=[C:2]([CH3:1])[CH:3]=3)[C:10]2=[O:12])[CH2:30][CH2:29][C:28](=[O:31])[NH:27]1

Participants

4

Reactant 2

HCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 669063973-(3-Methyl-benzyloxy)-phthalic acid

Product 1

HCID 250149692-(2,6-Dioxo-piperidin-3-yl)-4-(3-methyl-benzyloxy)-isoindole-1,3-dioneYield 49.6%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A mixture of 3-(3-methyl-benzyloxy)-phthalic acid (1.8 g, 6.4 mmol), alpha-amino-glutarimide hydrochloride (1.1 g, 6.8 mmol) in pyridine was refluxed overnight. The mixture was evaporated and the residue was purified by flash column chromatography (methanol/methylene chloride) to give 2-(2,6-dioxo-piperidin-3-yl)-4-(3-methyl-benzyloxy)-isoindole-1,3-dione as a white solid (1.2 g, 48% yield); HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 60/40 CH3CN/0.1% H3PO4, 3.16 min (99.9%); mp, 195-197° C.; 1H NMR (DMSO-d6) δ 2.00-2.07 (m, 1H, CHH), 2.33 (s, 3H, CH3), 2.54-2.62 (m, 2H, CH2), 2.83-2.95 (m, 1H, CHH), 5.10 (dd, J=6, 12 Hz, 1H, CH), 5.33 (s, 2H, CH2), 7.15-7.85 (m, 7H, Ar), 11.12 (s, 1H, NH); 13C NMR (DMSO-d6) δ 21.00, 21.96, 30.92, 48.74, 70.08, 115.49, 116.58, 120.19, 124.40, 127.85, 128.40, 128.60, 133.26, 136.03, 136.98, 137.64, 155.53, 165.30, 166.77, 169.91, 172.75. Anal Calcd For C21H18N2O5: C, 66.66; H, 4.79; N, 7.40. Found: C, 66.50; H, 4.79; N, 7.34.

Workup

  1. temperaturewas refluxed overnight
  2. customThe mixture was evaporated
  3. customthe residue was purified by flash column chromatography (methanol/methylene chloride)

Sources & evidence

ORD record
ord-890745cca0674d97b75eb9a6a55f224e
Source dataset
uspto-grants-2015_11
Patent number
US09181216B2

Linked notes

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