Methanol → 2-methoxy-N-[2-(3-methyl-2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]acetamide

HRID 2103546Notes

Reaction equation

HRID 2103546 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](=[O:21])[N:5]([C:12]1([CH3:20])[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19])[C:6]2=[O:11].[CH3:22][O:23][CH2:24][C:25](Cl)=[O:26].CO>C1COCC1>[CH3:22][O:23][CH2:24][C:25]([NH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](=[O:21])[N:5]([C:12]1([CH3:20])[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19])[C:6]2=[O:11])=[O:26]

Participants

5

Reactant 3

HCID 887MethanolHCID 96623Methoxyacetyl chlorideHCID 115220774-Amino-2-(3-methyl-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione

Product 1

HCID 219885352-methoxy-N-[2-(3-methyl-2,6-dioxo-3-piperidyl)-1,3-dioxo-isoindolin-4-yl]acetamideYield 88.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 4-amino-2-(3-methyl-2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione (0.10 g, 0.35 mmol) in THF (15 ml) was added methoxyacetyl chloride (0.08 g, 0.70 mmol). The mixture was heated to reflux for 6 hours. The reaction mixture was allowed to cool and to the solution was added methanol (2 ml). The reaction mixture was stirred for an additional 15 minutes followed by solvent evaporation in vacuo. The resulting solid was slurried in diethyl ether (20 ml) and filtered to give 0.111 g (87%) of product as an off-white solid: mp 244-246° C.; 1H NMR (DMSO-d6) 11.07 (s, 1H), 10.26 (s, 1H), 8.68 (d, J=8.3 Hz, 1H), 7.82 (t, J=7.7 Hz, 1H), 7.55 (d, J=7.2 Hz, 1H), 4.10 (s, 2H), 3.47 (s, 3H), 2.77-2.51 (m, 3H), 2.09-2.04 (m, 1H), 1.90 (s, 3H); 13C NMR (DMSO-d6) 172.12, 171.99, 169.15, 168.99, 167.38, 136.22, 135.68, 131.06, 124.25, 117.90, 115.91, 71.43, 59.06, 58.88, 29.01, 28.53, 20.92; Anal. Calcd. For C17H17N3O6: C, 56.48; H, 4.81; N, 11.62. Found: C, 56.10; H, 4.55; N, 11.39+0.12H2O.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 6 hours
  3. temperatureto cool and to the solution
  4. customfollowed by solvent evaporation in vacuo
  5. filtrationfiltered

Sources & evidence

ORD record
ord-3f171e8aaf6b47e381839cce2fe26ab5
Source dataset
uspto-grants-2009_08
Patent number
US07576104B2

Reaction notes

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