Acetyl chloride → 2-(4-chlorophenyl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile

HRID 1757600Notes

Reaction equation

HRID 1757600 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:16]#N)[NH:9][C:10](=O)[C:11]([F:14])([F:13])[F:12])=[CH:4][CH:3]=1.CS(O)(=O)=O.C(Cl)(=O)C.ClC(=C)[C:29]#[N:30].[CH2:32](N(CC)CC)C>C1(C)C=CC=CC=1.C(#N)C.O.CCCCCCC.C(OC(=O)C)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[NH:9][C:10]([C:11]([F:12])([F:13])[F:14])=[CH:32][C:16]=2[C:29]#[N:30])=[CH:6][CH:7]=1

Participants

11

Reactant 5

HCID 6367Acetyl chlorideHCID 6395Methanesulfonic AcidHCID 8471TriethylamineHCID 701982-ChloroacrylonitrileHCID 9903361N-(p-chloro-a-cyanobenzyl)-2,2,2-trifluoroacetamide

Product 1

HCID 110001432-(4-chlorophenyl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Conditions

Temperature
80 °C

Procedure

A slurry of N-[(p-chlorophenyl)cyanomethyl]-2,2,2-trifluoroacetamide (13.1 g, 0.05 mol) in toluene is treated sequentially with methanesulfonic acid (2.4 g, 0.025 mol) and acetyl chloride (4.32 g, 0.055 mol), at room temperature, heated at 80° C. for 2 hours, cooled to room temperature, diluted with acetonitrile, treated first with 2-chloroacrylonitrile (5.25 g, 0.06 mol) then dropwise with triethylamine (13.7 g, 0.135 mol), heated at 70°-72° C. for 1 hour, cooledto room temperature and diluted with water. The mixture is extracted with ethyl acetate. The extracts are combined, washed with water and concentrated in vacuo to give a residue. Flash chromatography (silica-gel;15% ethylacetate in heptane as eluent) gives the title product.

Workup

  1. temperaturecooled to room temperature
  2. customcooledto room temperature
  3. extractionThe mixture is extracted with ethyl acetate
  4. washwashed with water
  5. concentrationconcentrated in vacuo
  6. customto give a residue

Sources & evidence

ORD record
ord-a385f8009d6547e7b750cd21774f5244
Source dataset
uspto-grants-1995_08
Patent number
US05446170

Reaction notes

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