1-(Trifluoroacetyl)imidazole → 4-(4-fluorophenyl)-3-[4-(methylthio)phenyl]-5-(trifluoromethyl)-1H-pyrazole

HRID 375652Notes

Reaction equation

HRID 375652 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([C:11]2[CH:16]=[CH:15][C:14]([S:17][CH3:18])=[CH:13][CH:12]=2)=O)=[CH:4][CH:3]=1.C[Si]([N-:23][Si](C)(C)C)(C)C.[Li+].[F:29][C:30]([F:39])([F:38])[C:31]([N:33]1C=CN=C1)=O>O1CCCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([C:11]3[CH:16]=[CH:15][C:14]([S:17][CH3:18])=[CH:13][CH:12]=3)=[N:23][NH:33][C:31]=2[C:30]([F:39])([F:38])[F:29])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 737671-(Trifluoroacetyl)imidazoleHCID 2733832Lithium HexamethyldisilazideHCID 114709614-Fluorophenyl-1-[4-(methylthio)phenyl]ethanone

Product 1

HCID 153802214-(4-fluorophenyl)-3-[4-(methylthio)phenyl]-5-(trifluoromethyl)-1H-pyrazole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of 2-(4-fluorophenyl)-1-[4-(methylthio)phenyl]ethanone from Step 1 (11.53 g. 44 mmol) in 225 mL dry tetrahydrofuran (THF) was treated with 52.8 mL lithium bis(trimethylsilyl) amide (1.0M in THF) at -70° C. under nitrogen for 30 minutes and warmed to 0° C. for 30 minutes. Upon cooling to -70° C., a solution of 10.0 g (61 mmol) 1-trifluoroacetylimidazole in 25 mL THF was added and the mixture warmed to 0° C., during which time the solids dissolved. After 45 minutes, the reaction was quenched with saturated aqueous NH4Cl. The organic layer was diluted with ethyl acetate, washed sequentially with dilute HCl and brine, dried over MgSO4 and concentrated in vacuo. The crude mixture was washed with ether to remove unreacted starting ketone and the yellow solid (11.3 g) used without further purification. The crude mixture (11.3 g) was stirred with 60 mL glacial acetic acid and 4.5 mL hydrazine hydrane at reflux under nitrogen for 18 hours. The acetic acid was then removed in vacuo, and the residue dissolved in ethyl acetate, washed sequentially with dilute HCl and brine, dried over MgSO4 and reconcentrated in vacuo. Recrystallization from chloroform-hexane gave 8.24 g of the pyrazole as a pale yellow solid. Elemental analysis for C17H12N2F4S Calc'd.: C, 57.95, H, 3.43, N, 7.95, S, 9.10. Found: C, 57.58, H, 3.50, N, 7.88, S, 8.97.

Workup

  1. temperatureUpon cooling to -70° C.
  2. temperaturethe mixture warmed to 0° C., during which time the solids
  3. dissolutiondissolved
  4. customthe reaction was quenched with saturated aqueous NH4Cl
  5. additionThe organic layer was diluted with ethyl acetate
  6. washwashed sequentially with dilute HCl and brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. washThe crude mixture was washed with ether
  10. customto remove unreacted
  11. customthe yellow solid (11.3 g) used without further purification
  12. temperatureat reflux under nitrogen for 18 hours
  13. customThe acetic acid was then removed in vacuo
  14. dissolutionthe residue dissolved in ethyl acetate
  15. washwashed sequentially with dilute HCl and brine
  16. dry with materialdried over MgSO4
  17. customRecrystallization from chloroform-hexane

Sources & evidence

ORD record
ord-dc4587ec5aba4dcb80edf1fdc98578aa
Source dataset
uspto-grants-1996_01
Patent number
US05486534

Reaction notes

Loading…