Acetophenone → 3-(3-phenyl-1H-pyrazol-5-yl)propanenitrile

HRID 1471923Notes

Reaction equation

HRID 1471923 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)(=O)[CH3:2].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:20]([CH2:22][CH2:23][C:24](Cl)=O)#[N:21].O.[NH2:28][NH2:29]>C1(C)C=CC=CC=1.CCO.CC(O)=O>[C:4]1([C:1]2[CH:2]=[C:24]([CH2:23][CH2:22][C:20]#[N:21])[NH:29][N:28]=2)[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

8

Reactant 4

HCID 7410AcetophenoneHCID 24654Hydrazine hydrate (1:1)HCID 2733832Lithium HexamethyldisilazideHCID 128357153-Cyanopropanoyl chloride

Product 1

HCID 673847813-(3-phenyl-1H-pyrazol-5-yl)propanenitrileYield 30.5%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

To a solution of acetophenone (5.0 g, 41.6 mmol) in dry toluene (10 mL) was added LiHMDS (1.0 M in toluene) via syringe at 0° C. under argon. The reaction was allowed to stir at that temperature for 5 min and 3-cyanopropanoyl chloride (4.89 g, 41.6 mmol) was added via syringe in one portion. The ice bath was removed and AcOH (glacial, 5 mL), EtOH (100 mL), and hydrazine hydrate (6.25 g, 125 mmol) were added. The mixture was brought to reflux for 16 h. After cooled to room temperature, the reaction was concentrated, extracted with EtOAc, dried over MgSO4, and purified by column chromatography to give the title compound as yellowish oil (2.5 g). LCMS m/z=198.1 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.87 (t, J=4.42 Hz, 2H), 2.92 (t, J=4.04 Hz, 2H), 6.59 (s, 1H), 725-7.48 (m, 3H); 7.63-7.81 (m, 2H), 13.06 (bs, 1H).

Workup

  1. customThe ice bath was removed
  2. temperatureto reflux for 16 h
  3. concentrationthe reaction was concentrated
  4. extractionextracted with EtOAc
  5. dry with materialdried over MgSO4
  6. custompurified by column chromatography

Sources & evidence

ORD record
ord-4d742e762eba44dfbe01132eec7b238f
Source dataset
uspto-grants-2015_04
Patent number
US09012478B2

Reaction notes

Loading…