3-(Difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chloride → Fluxapyroxad

HRID 423437Notes

Reaction equation

HRID 423437 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[NH2:16])[CH:5]=[C:6]([F:9])[C:7]=1[F:8].[F:17][CH:18]([F:28])[C:19]1[C:23]([C:24](Cl)=[O:25])=[CH:22][N:21]([CH3:27])[N:20]=1>N1C=CC=CC=1>[F:28][CH:18]([F:17])[C:19]1[C:23]([C:24]([NH:16][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[C:4]2[CH:3]=[C:2]([F:1])[C:7]([F:8])=[C:6]([F:9])[CH:5]=2)=[O:25])=[CH:22][N:21]([CH3:27])[N:20]=1

Participants

4

Reactant 2

HCID 153401103-(Difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chlorideHCID 442492633,4,5-Trifluoro-2'-aminobiphenyl

Product 1

HCID 16095400FluxapyroxadYield 83%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
45 °C

Procedure

9.55 kg 3′,4′,5′-trifluoro[1,1′-biphenyl]-2-yl-amine (I) were dissolved in 51.4 kg and 6 kg pyridine were added. The mixture was stirred at 45° C. and 8.3 kg 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbonyl chloride (II) were dosed during one hour. Due to the exothermic nature of the reaction, the temperature raised to 55° C. Post-reaction by stirring for 1 hour at 55° C. followed. Three extractions at 85° C. with 16 liter hydrochloric acid (5%), 14 liter sodium hydrogen carbonate (8%), and 14 liter deionized water followed. The resulting clear solution in toluene was cooled from 85° C. with a rate of 10° C. per hour to 0° C. Around 75° C., the first turbidity was observed, and at 75° C. and 73° C., respectively, the batch was seeded with 10 g 3-(difluoromethyl)-1-methyl-N-(3′,4′,5′-trifluoro[1,1′-biphenyl]-2-yl)-1H-pyrazole-4-carboxamide (III) each (>98% form B). The resulting slurry was filtered at 0° C. over a process filter and the filter cake was washed with 10 kg toluene at 0° C. After drying in the drying cabinet at 80° C. and 20 mbar for 12 hours, 13.5 kg 3-(difluoromethyl)-1-methyl-N-(3′,4′,5′-trifluoro[1,1′-biphenyl]-2-yl)-1H-pyrazole-4-carboxamide (III) of >99.5% purity (GC, HPLC, NMR) was isolated. Using powder diffractometry (PXRD) and Fourier-Transform solid state infrared spectrometry (FT-IR) it was proven that the material consists to >98% of form B.

Workup

  1. additionwere added
  2. customDue to the exothermic nature of the reaction
  3. temperaturethe temperature raised to 55° C
  4. customPost-reaction
  5. stirringby stirring for 1 hour at 55° C.
  6. extractionThree extractions at 85° C. with 16 liter hydrochloric acid (5%), 14 liter sodium hydrogen carbonate (8%), and 14 liter
  7. temperatureThe resulting clear solution in toluene was cooled from 85° C. with a rate of 10° C. per hour to 0° C
  8. customAround 75° C.
  9. customat 75° C.
  10. custom73° C.
  11. filtrationThe resulting slurry was filtered at 0° C. over a process
  12. filtrationfilter
  13. washthe filter cake was washed with 10 kg toluene at 0° C
  14. customAfter drying in the drying cabinet at 80° C.

Sources & evidence

ORD record
ord-12b09cf781fb4e93850c3def2794ecb4
Source dataset
uspto-grants-2012_01
Patent number
US08101780B2

Reaction notes

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