Acetyl chloride → 1H-Pyrazole,3-methyl-5-phenyl-

HRID 1471876Notes

Reaction equation

HRID 1471876 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](Cl)(=O)[CH3:21].O.[NH2:25][NH2:26].[OH-].[Na+]>C1(C)C=CC=CC=1.CCO.CC(O)=O>[CH3:21][C:20]1[NH:26][N:25]=[C:1]([C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH:2]=1

Participants

9

Reactant 5

HCID 6367Acetyl chlorideHCID 7410AcetophenoneHCID 14798Sodium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 187741H-Pyrazole,3-methyl-5-phenyl-Yield 91.8%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

To a solution of acetophenone (10 g, 83 mmol) in anhydrous toluene (10 mL) was added LiHMDS (1.0 M in THF, 83 mL, 83 mmol) via syringe at 0° C. under argon. After 5 min, acetyl chloride (6.53 g, 83 mmol) was added via syringe in one portion. The ice bath was removed and AcOH (5 mL, glacial), EtOH (50 mL), and hydrazine hydrate (12.50 g, 250 mmol) were added. The mixture was refluxed for 2 h, cooled to room temperature, and neutralized to pH 7 by adding 1.0 M NaOH solution. The mixture was extracted with EtOAc, washed with brine, dried over MgSO4, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale yellow oil (12.05 g). LCMS m/z=159.0 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.25 (s, 3H), 6.42 (s, 1H), 7.20-7.44 (m, 3H), 7.67-7.82 (m, 2H), 12.53 (bs, 1H).

Workup

  1. customThe ice bath was removed
  2. temperatureThe mixture was refluxed for 2 h
  3. extractionThe mixture was extracted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-7770a04c7f9a4a1ab8b67c3ec260b5cb
Source dataset
uspto-grants-2015_04
Patent number
US09012478B2

Reaction notes

Loading…