Chloroacetyl chloride → 2-chloro-N-[2-(3-methyl-2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-acetamide

HRID 448508Notes

Reaction equation

HRID 448508 reaction equation
[Cl:1][CH2:2][C:3](Cl)=[O:4].[NH2:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[C:9](=[O:26])[N:10]([C:17]1([CH3:25])[CH2:22][CH2:21][C:20](=[O:23])[NH:19][C:18]1=[O:24])[C:11]2=[O:16]>C1COCC1>[Cl:1][CH2:2][C:3]([NH:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[C:9](=[O:26])[N:10]([C:17]1([CH3:25])[CH2:22][CH2:21][C:20](=[O:23])[NH:19][C:18]1=[O:24])[C:11]2=[O:16])=[O:4]

Participants

4

Reactant 2

HCID 6577Chloroacetyl chlorideHCID 115220774-Amino-2-(3-methyl-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione

Product 1

HCID 672293322-chloro-N-[2-(3-methyl-2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-acetamideYield 84.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Chloroacetyl chloride (0.9 g, 7.8 mmol) was added to a stirred suspension of 4-amino-2-(3-methyl-2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione (1.5 g, 5.2 mmol) in THF (20 mL). The mixture was refluxed for 30 minutes. The mixture was cooled to room temperature and filtered to give 2-chloro-N-[2-(3-methyl-2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-acetamide (1.6 g, 84%): 1H NMR (DSO-d6) δ 1.89 (s, 3H, CH3), 2.03-2.08 (m, 1H), 2.50-2.70 (m, 3H), 4.53 (s, 2H, CH2), 7.60 (d, J=7.3 Hz, 1H, Ar), 7.84 (t, J=7.7 Hz, 1H, Ar), 8.51 (d, J=8.4 Hz, 1H, Ar), 10.26 (s, 1H, NH), 11.05 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.98, 28.53, 29.04, 43.14, 58.89, 116.95, 118.54, 125.27, 131.30, 135.39, 136.16, 165.69, 167.31, 168.74, 171.98, 172.16.

Workup

  1. temperatureThe mixture was refluxed for 30 minutes
  2. filtrationfiltered

Sources & evidence

ORD record
ord-2daa9262892843be9399418d97862aa0
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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