Potassium Iodide → 4-{4-[4-(3,3-Dimethyl-butyl)-piperazin-1-yl]-butoxy}-3-fluoro-benzoic Acid Ethyl Ester

HRID 220911Notes

Reaction equation

HRID 220911 reaction equation
Cl.[CH3:2][C:3]([CH3:13])([CH3:12])[CH2:4][CH2:5][N:6]1[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[CH2:22]([O:24][C:25](=[O:39])[C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][CH2:35][CH2:36]Br)=[C:28]([F:38])[CH:27]=1)[CH3:23]>CC(C)=O>[CH2:22]([O:24][C:25](=[O:39])[C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][CH2:35][CH2:36][N:9]2[CH2:8][CH2:7][N:6]([CH2:5][CH2:4][C:3]([CH3:13])([CH3:12])[CH3:2])[CH2:11][CH2:10]2)=[C:28]([F:38])[CH:27]=1)[CH3:23]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 231123491-(3,3-Dimethyl-butyl)-piperazine hydrochlorideHCID 575552954-(4-Bromo-butoxy)-3-fluoro-benzoic Acid Ethyl Ester

Product 1

HCID 575553174-{4-[4-(3,3-Dimethyl-butyl)-piperazin-1-yl]-butoxy}-3-fluoro-benzoic Acid Ethyl EsterYield 90%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

1-(3,3-Dimethyl-butyl)-piperazine hydrochloride from Example E4 (874 mg, 3.7 mmol), potassium carbonate (2.5 g, 18.0 mmol) and potassium iodide (60 mg, 0.4 mmol) were added to a solution of 4-(4-bromo-butoxy)-3-fluoro-benzoic acid ethyl ester from Example E72.1 (1.4 g, 4.4 mmol) in acetone (35 ml) and the mixture was heated at reflux for 20 h. The solid was filtered off, washed with EtOAc and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; EtOAc to 1% 35% ammonia:10% methanol:89% EtOAc) to yield the title compound (1.35 g, 90%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 20 h
  3. filtrationThe solid was filtered off
  4. washwashed with EtOAc
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe residue was purified by flash chromatography on silica gel (eluant; EtOAc to 1% 35% ammonia:10% methanol:89% EtOAc)

Sources & evidence

ORD record
ord-05444b003f1a483cb2fc8d6a8e8c3f2e
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

Loading…