Acetoxyacetyl chloride → {N-[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]carbamovl}methyl acetate

HRID 9980

Reaction equation

HRID 9980 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].[C:21]([O:24][CH2:25][C:26](Cl)=[O:27])(=[O:23])[CH3:22]>C1COCC1>[C:21]([O:24][CH2:25][C:26](=[O:27])[NH: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])(=[O:23])[CH3:22]

Participants

4

Reactant 2

HCID 26297Acetoxyacetyl chlorideHCID 134780Pomalidomide

Product 1

HCID 10270658{N-[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]carbamovl}methyl acetateYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred suspension of 4-amino-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione (0.55 g, 2.0 mmol) in THF (30 ml) was added (chlorocarbonyl)methyl acetate (0.55 g, 4.0 mmol). The mixture was heated to reflux for 18 hours. The solvent was evaporated in vacuo and the resulting solid was slurried in diethyl ether (20 ml) and filtered to give 0.56 g (75%) of product as an off-white solid: mp 234–236° C.; 1H NMR (DMSO-d6) δ 11.15 (s, 1H), 10.06 (s, 1H), 8.55 (d, J=8.3 Hz, 1H), 7.87 (t, J=8.0 Hz, 1H), 7.65 (d, J=7.2 Hz, 1H), 5.17 (dd, J=5.0 and 12.4 Hz, 1H), 4.78 (s, 2H), 2.99–2.85 (m, 1H), 2.65–2.52 (m, 2H), 2.22 (s, 2H), 2.11–2.07 (m, 1H); 13C NMR (DMSO-d6) δ 172.70, 169.69, 169.50, 167.99, 166.57, 136.40, 135.59, 131.35, 125.34, 118.72, 116.96, 62.60, 48.98, 30.90, 21.91, 20.41; Anal. Calcd. For C17H15N3O7: C, 54.69; H, 4.05; N, 11.26. Found: C, 54.43; H, 4.05; N, 10.97.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 18 hours
  3. customThe solvent was evaporated in vacuo
  4. filtrationfiltered

Sources & evidence

ORD record
ord-c232326fe2bb4f1a9b4292d391209dba
Source dataset
uspto-grants-2006_08
Patent number
US07091353B2

Linked notes

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