Phenol → 1-[4-(2-Methoxyethoxy)phenyl]piperazine

HRID 986943Notes

Reaction equation

HRID 986943 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11](C(=O)C)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[H-].[Na+].C1(O)C=CC=CC=1.[CH3:26][O:27][CH2:28][CH2:29]Br>CN(C=O)C>[CH3:26][O:27][CH2:28][CH2:29][O:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 996PhenolHCID 24758Sodium hydrideHCID 809722-Bromoethyl methyl etherHCID 7124411-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone

Product 1

HCID 220249141-[4-(2-Methoxyethoxy)phenyl]piperazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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.

Workup

  1. concentrationconcentrate
  2. custompartition between EtOAc and 5% citric acid
  3. washWash the organic with 1N NaOH
  4. dry with materialDry over MgSO4
  5. concentrationconcentrate

Sources & evidence

ORD record
ord-2110df1a41db4f87b5d2e42e8ecb7d18
Source dataset
uspto-grants-2003_10
Patent number
US06630475B2

Reaction notes

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