Methyl iodide → 3-(2,5-difluorophenyl)-1,4-dimethyl-5-(trifluoromethyl)-1H-pyrazole

HRID 1378291Notes

Reaction equation

HRID 1378291 reaction equation
Br[C:2]1[C:3]([C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=2[F:19])=[N:4][N:5]([CH3:11])[C:6]=1[C:7]([F:10])([F:9])[F:8].[CH2:20]([Li])CCC.CI>C1COCC1>[F:19][C:13]1[CH:14]=[CH:15][C:16]([F:18])=[CH:17][C:12]=1[C:3]1[C:2]([CH3:20])=[C:6]([C:7]([F:10])([F:9])[F:8])[N:5]([CH3:11])[N:4]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 110569594-bromo-3-(2,5-difluorophenyl)-1-methyl-5-(trifluoromethyl)-1H-pyrazoleHCID 178418339Butyllithium

Product 1

HCID 110656733-(2,5-difluorophenyl)-1,4-dimethyl-5-(trifluoromethyl)-1H-pyrazoleYield 72.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 10 g of 4-bromo-3-(2,5-difluorophenyl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole in 250 mL anhydrous THF was cooled to -78° C. and stirred with an overhead stirrer. The cold solution was treated with 12 mL of 2.5M n-butyllithium in hexanes never allowing the temperature to exceed -70° C. After stirring for 5 minutes, 1.9 mL of methyl iodide was added quickly. The cooling bath was removed and the solution allowed to warm to room temperature. The solution was diluted with diethyl ether and the combined organic extracts were washed twice with brine, dried over anhydrous magnesium sulfate and concd in vacuo. Chromatographic purification (silica, 5% ethyl acetate in hexanes) gave 5.8 g (72.4%) of 3-(2,5-difluorophenyl)-1,4-dimethyl-5-(trifluoromethyl)-1H-pyrazole as an oil; 1HNMR (CDCl3) δ 2.0 (quintet, 3H, J=2.1 Hz), 3.9 (d, 3H, J=1.2 Hz), 6.9-7.1 (m, 3H). Anal. Calcd for C13H9F5N2: C, 52.18; H, 3.28; N, 10.14. Found: C, 52.20; H, 3.30; N, 10.11.

Workup

  1. customto exceed -70° C
  2. stirringAfter stirring for 5 minutes
  3. customThe cooling bath was removed
  4. additionThe solution was diluted with diethyl ether
  5. washthe combined organic extracts were washed twice with brine
  6. dry with materialdried over anhydrous magnesium sulfate and concd in vacuo
  7. customChromatographic purification (silica, 5% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-3e9ef4cf57294a5a9fc0b5fd42fda641
Source dataset
uspto-grants-1997_09
Patent number
US05668088

Reaction notes

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