Triethylamine → 4-(4-(2-Tert-butyl-phenyl)piperazin-1-yl)-4-oxobutanenitrile

HRID 534915Notes

Reaction equation

HRID 534915 reaction equation
[C:1]([CH2:3][CH2:4][C:5]([OH:7])=O)#[N:2].C(Cl)(=O)C(Cl)=O.[C:14]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1)([CH3:17])([CH3:16])[CH3:15].C(N(CC)CC)C.C(CCC(Cl)=O)#N>CN(C=O)C.C1COCC1.C(Cl)Cl>[C:14]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[N:24]1[CH2:29][CH2:28][N:27]([C:5](=[O:7])[CH2:4][CH2:3][C:1]#[N:2])[CH2:26][CH2:25]1)([CH3:17])([CH3:15])[CH3:16]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 2630863-Cyanopropanoic acidHCID 128357153-Cyanopropanoyl chlorideHCID 469416591-(2-Tert-butylphenyl)piperazine

Product 1

HCID 667510584-(4-(2-Tert-butyl-phenyl)piperazin-1-yl)-4-oxobutanenitrileYield 57%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution at 0° C. of provide 3-cyanopropanoic acid (0.110 g, 1.11 mmol) and DMF (2 drops) in THF (4.0 mL) was added oxalyl chloride (0.144 g, 1.13 mmol) dropwise and the reaction mixture was warmed to room temperature. After 1 h the reaction mixture was concentrated under reduced pressure. To a stirred solution at 0° C. of 1-(2-tert-butylphenyl)piperazine (0.218 g, 1.00 mmol) and triethylamine (0.303 g, 3.00 mmol) in methylene chloride (2.0 mL) was added a solution of the freshly prepared 3-cyanopropanoyl chloride in methylene chloride (2.0 mL) and the reaction mixture was warmed to room temperature. After 2 h the reaction mixture was diluted with methylene chloride (10.0 mL), washed with water (20.0 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, 50% ethyl acetate/heptanes) to provide 4-(4-(2-tert-butyl-phenyl)piperazin-1-yl)-4-oxobutanenitrile (0.170 g, 57%) as an off-white solid, mp 109-110° C.

Workup

  1. concentrationAfter 1 h the reaction mixture was concentrated under reduced pressure
  2. temperaturethe reaction mixture was warmed to room temperature
  3. washwashed with water (20.0 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash column chromatography (silica gel, 50% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-6ad2177aee864b498c2c4184b0381252
Source dataset
uspto-grants-2014_10
Patent number
US08853215B2

Reaction notes

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