Acetonitrile → 3-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-3-oxopropanenitrile

HRID 1893723Notes

Reaction equation

HRID 1893723 reaction equation
[Li]CCCC.[C:6](#[N:8])[CH3:7].[CH3:9][O:10][C:11]1[CH:27]=[CH:26][C:14]([CH2:15][N:16]2[CH:20]=[C:19]([C:21]([O:23]CC)=O)[CH:18]=[N:17]2)=[CH:13][CH:12]=1>C1COCC1>[CH3:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([CH2:15][N:16]2[CH:20]=[C:19]([C:21](=[O:23])[CH2:7][C:6]#[N:8])[CH:18]=[N:17]2)=[CH:26][CH:27]=1

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 44558860ethyl 1-(4-methoxybenzyl)-1H-pyrazole-4-carboxylateHCID 178418339Butyllithium

Product 1

HCID 666687013-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-3-oxopropanenitrileYield 68.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

According to Scheme 7, Step 1: At −78° C., BuLi (23 mmol, 9.2 mL, 2.5M) was added dropwise to a solution of acetonitrile (21.1 mmol, 0.87 g) in THF (25 mL). The resulting mixture was stirred at this temperature for 20 minutes and then ethyl 1-(4-methoxybenzyl)-1H-pyrazole-4-carboxylate (19.2 mmol, 5.00 g) in THF (25 mL) was added. The reaction mixture was stirred at −78° C. for 1 hour and then allowed to warm up to room temperature and stirred for another 1 hour. The reaction was quenched with saturated NH4Cl aqueous solution and extracted with EtOAc (50 mL×3). The combined organic phases were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified on combi-flash EtOAc/PE (1:15 to ˜1:5) to give 3-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-3-oxopropanenitrile (13.1 mmol, 3.33 g, 68%).

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for 1 hour
  2. stirringstirred for another 1 hour
  3. customThe reaction was quenched with saturated NH4Cl aqueous solution
  4. extractionextracted with EtOAc (50 mL×3)
  5. dry with materialThe combined organic phases were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified on combi-flash EtOAc/PE (1:15 to ˜1:5)

Sources & evidence

ORD record
ord-f9eb56fe53ba43d48e791d3470649dd4
Source dataset
uspto-grants-2013_08
Patent number
US08513252B2

Reaction notes

Loading…