Methyl chlorodifluoroacetate → 3-n-Butyl-4-[(3-fluoro-2'-sulfamoylbiphenyl-4-yl)methyl]-1-[5-nitro-2-(trifluoromethyl)phenyl]-1H-pyrazole-5-carbonitrile

HRID 257585Notes

Reaction equation

HRID 257585 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[N:11]1[C:15]([C:16]#[N:17])=[C:14]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[S:31](=[O:34])(=[O:33])[NH2:32])=[CH:21][C:20]=2[F:35])[C:13]([CH2:36][CH2:37][CH2:38][CH3:39])=[N:12]1.Cl[C:41]([F:47])([F:46])C(OC)=O.[F-:48].[K+].[Br-].[K+]>O.CN(C=O)C>[CH2:36]([C:13]1[C:14]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[S:31](=[O:34])(=[O:33])[NH2:32])=[CH:21][C:20]=2[F:35])=[C:15]([C:16]#[N:17])[N:11]([C:3]2[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=2[C:41]([F:47])([F:48])[F:46])[N:12]=1)[CH2:37][CH2:38][CH3:39]

Participants

7

Reactant 4

HCID 73935Methyl chlorodifluoroacetateHCID 253877Potassium BromideHCID 522689Potassium FluorideHCID 197831611-(2-Bromo-5-nitrophenyl)-3-n-butyl-4-[(3-fluoro-2'-sulfamoylbiphenyl-4-yl)methyl]-1H-pyrazole-5-carbonitrile

Product 1

HCID 197831703-n-Butyl-4-[(3-fluoro-2'-sulfamoylbiphenyl-4-yl)methyl]-1-[5-nitro-2-(trifluoromethyl)phenyl]-1H-pyrazole-5-carbonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1-(2-bromo-5-nitrophenyl)-3-n-butyl-4-[(3-fluoro-2'-sulfamoylbiphenyl-4-yl)methyl]-1H-pyrazole-5-carbonitrile (from Step A) (1 equivalent), methyl chlorodifluoroacetate (2 equiv), potassium fluoride (1 equiv), cuprous iodide (1 equiv), potassium bromide (1 equiv), and DMF (approximately 3 mL per gram of pyrazole compound) is stirred under N2 in a sealed tube at 120° C. for about 15 hours. The cooled mixture is diluted with H2O and extracted a few times with ethyl acetate. The combined organic fractions are washed with brine, dried over Na2SO4, and filtered. The filtrate is concentrated, and the residue is chromatographed on silica gel (elution with CH2Cl2 --MeOH) to yield the title compound.

Workup

  1. extractionextracted a few times with ethyl acetate
  2. washThe combined organic fractions are washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationThe filtrate is concentrated
  6. customthe residue is chromatographed on silica gel (elution with CH2Cl2 --MeOH)

Sources & evidence

ORD record
ord-72e6e1a6b52e43d8bfe826d769fae8a3
Source dataset
uspto-grants-1993_11
Patent number
US05262412

Reaction notes

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