Triethylamine → Fluxapyroxad

HRID 1692040Notes

Reaction equation

HRID 1692040 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=2[NH2:12])[CH:5]=[C:6]([F:9])[C:7]=1[F:8].C(N(CC)CC)C.[C:24](=[O:27])([O-])[O-].[K+].[K+].Br[C:31]1[C:32]([CH:37]([F:39])[F:38])=[N:33][N:34]([CH3:36])[CH:35]=1>C(#N)C.[Pd](Cl)Cl.CC(C)(CP(C1C=CC=CC=1)C1C=CC=CC=1)CP(C1C=CC=CC=1)C1C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=2[NH:12][C:24]([C:31]2[C:32]([CH:37]([F:39])[F:38])=[N:33][N:34]([CH3:36])[CH:35]=2)=[O:27])[CH:5]=[C:6]([F:9])[C:7]=1[F:8]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 442492633,4,5-Trifluoro-2'-aminobiphenylHCID 442492644-Bromo-3-(difluoromethyl)-1-methyl-1H-pyrazole

Product 1

HCID 16095400FluxapyroxadYield 57.5%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 16744767(2,2-Dimethylpropane-1,3-diyl)bis(diphenylphosphane)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
130 °C

Procedure

In an autoclave, 2-(3,4,5-trifluorophenyl)aniline (5.29 g, 23.7 mmol), triethylamine (1.20 g, 11.8 mmol), palladium chloride (86 mg, 0.47 mmol), anhydrous potassium carbonate (6.55 g, 47.4 mmol) and 2,2-dimethyl-1,3-bis(diphenylphosphino)propane (313 mg, 0.71 mmol) were added to a solution of 4-bromo-3-difluoromethyl-1-methylpyrazole (5.00 g, 23.7 mmol) in acetonitrile (100 ml). The autoclave was flushed three times with 9 bar of nitrogen and then 3 times with 10 bar of carbon monoxide. The reaction mixture was stirred under a carbon monoxide pressure of 9 mbar at an external temperature of 130° C. for 20 h. The red-brown suspension obtained after cooling and venting was filtered, and the filtrate was freed from volatile components under reduced pressure. The residue was taken up in a mixture of tetrahydrofuran (60 ml) and methyl tert-butyl ether (MTBE, 60 ml), washed twice with hydrochloric acid (5% strength, in each case 40 ml) and once with water (30 ml), dried over sodium sulfate and filtered, and the solvent was removed under reduced pressure. The residue was triturated with diisopropyl ether (20 ml), and the solid was filtered off and dried under reduced pressure. 5.20 g (yield 54%) of N-(2-(3,4,5-trifluorophenyl)phenyl)-3-difluoromethyl-1-methylpyrazole-4-carboxamide were isolated in a purity of 93%, according to HPLC analysis (Merck Chromolith SpeedROD RP-18e column, 50×4.6 mm; gradient: acetonitrile/water with 0.1% trifluoroacetic acid, 7 min from 10% to 95% acetonitrile).

Workup

  1. customThe autoclave was flushed three times with 9 bar of nitrogen
  2. customThe red-brown suspension obtained
  3. temperatureafter cooling
  4. filtrationventing was filtered
  5. additionThe residue was taken up in a mixture of tetrahydrofuran (60 ml) and methyl tert-butyl ether (MTBE, 60 ml)
  6. washwashed twice with hydrochloric acid (5% strength
  7. dry with materialin each case 40 ml) and once with water (30 ml), dried over sodium sulfate
  8. filtrationfiltered
  9. customthe solvent was removed under reduced pressure
  10. customThe residue was triturated with diisopropyl ether (20 ml)
  11. filtrationthe solid was filtered off
  12. customdried under reduced pressure

Sources & evidence

ORD record
ord-d05299346b6d4049bfa08ca5b0ecdde3
Source dataset
uspto-grants-2012_04
Patent number
US08153820B2

Reaction notes

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