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

HRID 906730Notes

Reaction equation

HRID 906730 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4](=[O:20])[N:5]([CH:12]1[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19])[C:6]2=[O:11].[Cl:21][CH2:22][C:23](Cl)=[O:24]>C1COCC1>[O:19]=[C:13]1[CH:12]([N:5]2[C:4](=[O:20])[C:3]3[C:7](=[CH:8][CH:9]=[CH:10][C:2]=3[NH:1][C:23](=[O:24])[CH2:22][Cl:21])[C:6]2=[O:11])[CH2:17][CH2:16][C:15](=[O:18])[NH:14]1

Participants

4

Reactant 2

HCID 6577Chloroacetyl chlorideHCID 134780Pomalidomide

Product 1

HCID 10154850Acetamide, 2-chloro-N-[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]-Yield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred suspension of 4-amino-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione (1.37 g, 5.00 mmol) in THF (30 ml) was added chloroacetyl chloride-(0.62 g, 5.5 mmol). The mixture was heated to reflux for 30 minutes. The solvent was evaporated in vacuo and the resulting solid was slurried in diethyl ether (20 ml) and filtered to give 1.67 g (96%) of product as an off-white solid: 1H NMR (DMSO-d6) δ 11.18 (s, 1H), 10.31 (s, 1H), 8.54 (d, J=8.4 Hz, 1H), 7.88 (t, J=7.7 Hz, 1H), 7.68 (d, J=7.3 Hz, 1H), 5.17 (dd, J=5.2 and 12.7 Hz, 1H), 4.54 (s, 2H), 2.90-2.85 (m, 1H), 2.65-2.51 (m, 2H), 2.10-2.06 (m, 1H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 30 minutes
  3. customThe solvent was evaporated in vacuo
  4. filtrationfiltered

Sources & evidence

ORD record
ord-ede81cc24e7d44019b44017ae0fc4c15
Source dataset
uspto-grants-2011_09
Patent number
US08012997B2

Reaction notes

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