Chloroacetyl chloride → 2-chloro-N-[2-(2,6-dioxo-3-piperidyl)-1-oxo-isoindolin-4-yl]acetamide

HRID 906732

Reaction equation

HRID 906732 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][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:20][CH2:21][C:22](Cl)=[O:23]>C1COCC1.ClCC(Cl)=O>[O:19]=[C:13]1[CH:12]([N:5]2[CH2:4][C:3]3[C:7](=[CH:8][CH:9]=[CH:10][C:2]=3[NH:1][C:22](=[O:23])[CH2:21][Cl:20])[C:6]2=[O:11])[CH2:17][CH2:16][C:15](=[O:18])[NH:14]1

Participants

5

Reactant 2

HCID 6577Chloroacetyl chlorideHCID 216326Lenalidomide

Product 1

HCID 98808592-chloro-N-[2-(2,6-dioxo-3-piperidyl)-1-oxo-isoindolin-4-yl]acetamideYield 92.1%

Reagents, catalysts & solvents 2

HCID 6577Chloroacetyl chlorideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred suspension of 3-(4-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione (3.89 g, 15.0 mmol) in THF (50 ml) was added chloroacetyl chloride (1.86 g, 16.5 mmol). The mixture was heated to reflux for 45 minutes. To the reaction mixture was added additional chloroacetyl chloride (0.15 g, 0.13 mmol). The reaction mixture was heated at reflux for an additional 30 minutes. The solvent was evaporated in vacuo and the resulting solid was slurried in diethyl ether (20 ml) and filtered to give 4.64 g (92%) of product as an off-white solid: 1H NMR (DMSO-d6) δ 11.04 (s, 1H), 10.22 (s, 1H), 7.82 (dd, J=1.6 and 7.2 Hz, 1H), 7.59-7.50 (m, 2H), 5.16 (dd, J=5.1 and 13.2 Hz, 1H), 4.46-4.30 (m, 4H), 3.00-2.85 (m, 1H), 2.65-2.58 (m, 1H), 2.44-2.28 (m, 1H), 2.06-2.01 (m, 1H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 45 minutes
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux for an additional 30 minutes
  5. customThe solvent was evaporated in vacuo
  6. filtrationfiltered

Sources & evidence

ORD record
ord-2f31041a412e47b9932d8caa83b39814
Source dataset
uspto-grants-2011_09
Patent number
US08012997B2

Linked notes

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