Potassium Iodide → Ethyl 3-[4-(2-methoxyphenyl)piperazin-1-yl]butanoate

HRID 1514162Notes

Reaction equation

HRID 1514162 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.Br[CH:17]([CH3:24])[CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(#N)C.O>[CH3:2][O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]1[CH2:15][CH2:14][N:13]([CH:17]([CH3:24])[CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:12][CH2:11]1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 95424Butanoic acid, 3-bromo-, ethyl esterHCID 9899402N-(2-Methoxyphenyl)piperazine hydrochloride

Product 1

HCID 59536458Ethyl 3-[4-(2-methoxyphenyl)piperazin-1-yl]butanoateYield 42%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A slurry of 1-(2-methoxyphenyl)piperazine hydrochloride (5 g, 21.86 mmol), ethyl 3-bromobutyrate (4.48 g, 22.96 mmol), potassium carbonate (10.57 g, 76.51 mmol) and a catalytic amount of potassium iodide (0.362 g, 2.18 mmol) in acetonitrile (50 mL) was heated at reflux for 18 hrs. After cooling at room temperature, the reaction mixture was added to water (100 mL) and the aqueous phase was extracted with AcOEt (100 mL). The organic phase was washed with water (2×75 mL), brine (75 mL), dried over MgSO4 and evaporated to dryness. The resulting light yellow oil was purified by flash chromatography (Biotage Isolute SI, 40 g column, gradient hexane to 33% ethyl acetate in hexane) and afforded 2.8 g (42%) ethyl 3-[4-(2-methoxyphenyl)piperazin-1-yl]butanoate D11 as a colourless oil.

Workup

  1. temperatureat reflux for 18 hrs
  2. extractionthe aqueous phase was extracted with AcOEt (100 mL)
  3. washThe organic phase was washed with water (2×75 mL), brine (75 mL)
  4. dry with materialdried over MgSO4
  5. customevaporated to dryness
  6. customThe resulting light yellow oil was purified by flash chromatography (Biotage Isolute SI, 40 g column, gradient hexane to 33% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-e9a14abfcaa14ea28a163b3ef3567564
Source dataset
uspto-grants-2012_07
Patent number
US08222254B2

Reaction notes

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