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

HRID 906782Notes

Reaction equation

HRID 906782 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 87.5%

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 (1-5 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 0.11 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-77f7aa271f3e44c79ef38cd8208aa4fe
Source dataset
uspto-grants-2011_09
Patent number
US08012997B2

Reaction notes

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