Acrylonitrile → 1-(4-Methoxy-benzyl)-1H-pyrazol-2-ylamine

HRID 2261195Notes

Reaction equation

HRID 2261195 reaction equation
[C:1](#[N:4])[CH:2]=[CH2:3].O.[NH2:6][NH2:7].[CH:8](=O)[C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1.C(O[Na])CCC>C1COCC1.CCCCO.O>[CH3:16][O:15][C:12]1[CH:13]=[CH:14][C:9]([CH2:8][N:4]2[CH:1]=[CH:2][CH2:3][N:6]2[NH2:7])=[CH:10][CH:11]=1

Participants

8

Reactant 4

HCID 7855AcrylonitrileHCID 24654Hydrazine hydrate (1:1)HCID 312444-MethoxybenzaldehydeHCID 178454433HCID 178454433, compound

Product 1

HCID 669169241-(4-Methoxy-benzyl)-1H-pyrazol-2-ylamine

Reagents, catalysts & solvents 3

HCID 2631-ButanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Acrylonitrile (7.5 g, 141 mmol) is dissolved in THF (75 mL) and cooled at 0° C. and hydrazine monohydrate (7.41 g, 148 mmol) is added at the same temperature. The reaction mixture is brought to room temperature and stirred for 2 h. p-Anisaldehyde (20.1 g, 148 mmol) is added drop wise and stirred at room temperature for 10 h. The above reaction mixture is then concentrated to result red oil. To the above oil n-BuONa in 80 mL n-BuOH is added drop wise at 0° C. and brought to room temperature. The reaction mixture is heated at 120° C. for 3.5 h. After cooling it is poured onto 300 mL of cold water and extracted with 2×200 mL of Et2O. The ether layer is collected and washed with 3×100 mL of 1N HCl. The combined acidic layer is collected and neutralized with 50% NaOH. The mixture is again extracted with 200 mL of Et2O and washed with water. It is dried (Na2SO4) and concentrated to yield 1-(4-Methoxy-benzyl)-1H-pyrazol-2-ylamine as red oil. MS m/z 204.1 (M+1). Mixture of 1-(4-methoxy-benzyl)-1H-pyrazol-2-ylamine (1 g, 5.0 mmol) and diethyl ethoxymethylenemalonate (1 mL, 5.0 mmol) is heated at 120° C. for 5 h. It is cooled and then the desired compound is isolated by silica gel column chromatography. MS m/z 374.2 (M+1).

Workup

  1. customis brought to room temperature
  2. additionis added drop wise
  3. customThe above reaction mixture
  4. concentrationis then concentrated
  5. customto result red oil
  6. custombrought to room temperature
  7. temperatureThe reaction mixture is heated at 120° C. for 3.5 h
  8. temperatureAfter cooling it
  9. extractionextracted with 2×200 mL of Et2O
  10. customThe ether layer is collected
  11. washwashed with 3×100 mL of 1N HCl
  12. customThe combined acidic layer is collected
  13. extractionThe mixture is again extracted with 200 mL of Et2O
  14. washwashed with water
  15. dry with materialIt is dried (Na2SO4)
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-3afb284d026a4571a462a83747e3bee9
Source dataset
uspto-grants-2010_12
Patent number
US07846923B2

Reaction notes

Loading…