1,2-Dichloroethane → 3-[4-(4-Fluorobenzyl)-3-oxopiperazin-1-yl]-3-oxopropanenitrile

HRID 2109841Notes

Reaction equation

HRID 2109841 reaction equation
[F:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][NH:10][CH2:9][C:8]2=[O:13])=[CH:4][CH:3]=1.[C:16]([CH2:18][C:19](O)=[O:20])#[N:17].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.C(N(CC)C(C)C)(C)C>[F:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][N:10]([C:19](=[O:20])[CH2:18][C:16]#[N:17])[CH2:9][C:8]2=[O:13])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 9740Cyanoacetic acidHCID 757711-HydroxybenzotriazoleHCID 185386381-(4-Fluorobenzyl)piperazin-2-one

Product 1

HCID 576346353-[4-(4-Fluorobenzyl)-3-oxopiperazin-1-yl]-3-oxopropanenitrile

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 81531DiisopropylethylamineSolvent

Procedure

To a solution of 1-(4-fluorobenzyl)piperazin-2-one (1.99 g, 9.6 mmol), cyanoacetic acid (0.82 g, 9.6 mmol), EDC (2.02 g, 10.5 mmol), and HOBt (0.15 g, 0.96 mmol) in anhydrous DMF (40 mL), N,N-diisopropylethylamine was added until the solution is about pH 6. The reaction mixture was stirred at room temperature overnight and concentrated under vacuum. The residue was partitioned between chloroform and water. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum to provide the title compound. The residue was subjected to column chromatography on silica gel eluting with a mixture of 9:1:0.1 mixture of chloroform, methanol, and aq ammonium hydroxide. Collection and concentration of appropriate fractions provided the title product. Residual protic solvent was removed by co-evaporation with benzene (3×). ES MS M-OCH3=276

Workup

  1. concentrationconcentrated under vacuum
  2. customThe residue was partitioned between chloroform and water
  3. extractionThe organic extract
  4. washwas washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-7fa23def3d8c4bfdb17deff5fa72b33d
Source dataset
uspto-grants-2009_04
Patent number
US07517532B2

Reaction notes

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