Trifluoromethanesulfonic acid → 2-(4-chlorophenyl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile

HRID 1290224Notes

Reaction equation

HRID 1290224 reaction equation
[Cl:1][C:2]1[CH:17]=[CH:16][C:5]([CH:6]([NH:9][C:10](=O)[C:11]([F:14])([F:13])[F:12])[C:7]#N)=[CH:4][CH:3]=1.FC(F)(F)S(O)(=O)=O.[NH2:26][C:27]1OC=NC=1.Cl[C:33](=C)C#N>O.C(OCC)(=O)C.CN(C)C=O.C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]2[NH:9][C:10]([C:11]([F:12])([F:13])[F:14])=[CH:33][C:7]=2[C:27]#[N:26])=[CH:16][CH:17]=1

Participants

9

Reactant 4

HCID 62406Trifluoromethanesulfonic acidHCID 701982-ChloroacrylonitrileHCID 9903361N-(p-chloro-a-cyanobenzyl)-2,2,2-trifluoroacetamideHCID 212170945-Aminooxazole

Product 1

HCID 110001432-(4-chlorophenyl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrileYield 57%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of N-(p-chloro-α-cyanobenzyl)-2,2,2-tri-fluoroacetamide (10.5 g, 0.04 mol) and toluene is cooled to 5°-10° C. under a nitrogen atmosphere, treated with trifluoromethanesulfonic acid (12.0 g, 0.08 mol) over a 20 minute period, allowed to warm to room temperature and held at 25° C. for 3 hours. The formation of the intermediate 5-amino oxazole salt is monitored by 19F NMR (DMSO-d6). When the intermediate salt formation is complete, the mixture is cooled below 20° C., treated with dimethylformamide and 2-chloroacrylonitrile (5.25 g, 0.06 mol), held at 25° C. for 16-18 hours, and treated with ethyl acetate and water. The phases are separated and the organic phase is washed with water and concentrated in vacuo to give a solid residue. Flash column chromatography of the residue on silica gel, packed and eluted respectively with 15% and 20% ethyl acetate in heptane gives the title product as pale yellow crystals, 6.14 g (57% yield), mp 237°-240° C., identified by HPLC and NMR analyses.

Workup

  1. temperatureis cooled to 5°-10° C. under a nitrogen atmosphere
  2. temperaturethe mixture is cooled below 20° C.
  3. waitheld at 25° C. for 16-18 hours
  4. customThe phases are separated
  5. washthe organic phase is washed with water
  6. concentrationconcentrated in vacuo
  7. customto give a solid residue
  8. washeluted respectively with 15% and 20% ethyl acetate in heptane

Sources & evidence

ORD record
ord-303b171a20cd4e9b9f90df73dee8351f
Source dataset
uspto-grants-1998_05
Patent number
US05750726

Reaction notes

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