Potassium Iodide → 4-[3-(4-Cyclopropyl-piperazin-1-yl)-propoxy]-3-fluoro-benzoic Acid Ethyl Ester

HRID 220869Notes

Reaction equation

HRID 220869 reaction equation
Cl.Cl.[CH:3]1([N:6]2[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]2)[CH2:5][CH2:4]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[CH2:20]([O:22][C:23](=[O:36])[C:24]1[CH:29]=[CH:28][C:27]([O:30][CH2:31][CH2:32][CH2:33]Br)=[C:26]([F:35])[CH:25]=1)[CH3:21]>CC(C)=O>[NH3:6].[CH2:20]([O:22][C:23](=[O:36])[C:24]1[CH:29]=[CH:28][C:27]([O:30][CH2:31][CH2:32][CH2:33][N:9]2[CH2:10][CH2:11][N:6]([CH:3]3[CH2:5][CH2:4]3)[CH2:7][CH2:8]2)=[C:26]([F:35])[CH:25]=1)[CH3:21]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 212208121-Cyclopropylpiperazine dihydrochlorideHCID 575553074-(3-Bromo-propoxy)-3-fluorobenzoic acid ethyl ester

Product 2

HCID 222AmmoniaHCID 575554304-[3-(4-Cyclopropyl-piperazin-1-yl)-propoxy]-3-fluoro-benzoic Acid Ethyl EsterYield 89%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

1-Cyclopropyl-piperazine dihydrochloride (642 mg, 3.2 mmol, according to the procedure described by G. S. Poindexter, M. A. Bruce, K. L. Le Boulluec, I. Monkovic, Tet. Lett., 35(44), 7331-7334, 1994), potassium carbon-ate (2.1 g, 15.2 mmol) and potassium iodide (50 mg, 0.3 mmol) were added to 4-(3-bromo-propoxy)-3-fluoro-benzoic acid ethyl ester from Example E48.1 (1.2 g, 3.9 mmol) in acetone (25 ml). 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 then 1% 35% ammonia:9% methanol:90% dichloromethane) to yield the title compound (1.0 g, 89%).

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

Sources & evidence

ORD record
ord-c98fd37e81ea4f8f8f44c42142e3838d
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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