Reaction #10084

Reaction equation

3-(4-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione

chloroacetyl chloride

→

product

Yield 92.1%

N-[2-(2,6-dioxo(3-piperidyl))-1-oxoisoindolin-4-yl]-2-chloroacetamide

Yield 92.1%

Solvents

THF

Conditions

Workup

1. 1
   TemperatureThe mixture was heated
2. 2
   Temperatureto reflux for 45 minutes
3. 3
   TemperatureThe reaction mixture was heated
4. 4
   Temperatureat reflux for an additional 30 minutes
5. 5
   OtherThe solvent was evaporated in vacuo
6. 6
   Filtrationfiltered

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).

Source