Reaction #2175418

Reaction equation

4-(4-hydroxy-phenyl)-1-acetylpiperazine

NaH

phenol

2-bromoethyl methyl ether

→

1-(4-(2-Methoxyethoxy)phenyl)piperazine

Solvents

DMF

Conditions

Workup

1. 1
   Concentrationconcentrate
2. 2
   Otherpartition between EtOAc and 5% citric acid
3. 3
   WashWash the organic with 1N NaOH
4. 4
   DryingDry over MgSO4
5. 5
   Concentrationconcentrate

Procedure

1-(4-(2-Methoxyethoxy)phenyl)piperazine is prepared from 4-(4-hydroxy-phenyl)-1-acetylpiperazine. To NaH (60% in mineral oil, 0.79 g, 20 mmol) in DMF (25 ml) add the phenol (3.0 g, 13.6 mmol), followed by 2-bromoethyl methyl ether (2.27 g, 16.3 mmol). Stir at RT 18 h, concentrate, and partition between EtOAc and 5% citric acid. Wash the organic with 1N NaOH, then brine. Dry over MgSO4, and concentrate to obtain the alkylated product as a white solid. Heat this material (2.2 g, 7.9 mmol) in 6N HCl (30 ml) at reflux for 1 h. Allow to cool and basify to pH=10 with NaOH. Extract with CH2Cl2 and wash with water and then brine. Dry the organic with MgSO4 and concentrate to give the piperazine as a yellow oil.

Source