Ethyl Acetate → 2-(4-chlorophenyl)-1-methyl-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile

HRID 1290226Notes

Reaction equation

HRID 1290226 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]([CH:6]([N:9]([CH3:16])[C:10](=O)[C:11]([F:14])([F:13])[F:12])[C:7]#N)=[CH:4][CH:3]=1.ClC(=C)[C:21]#[N:22].[C:24](OCC)(=O)C>C1(C)C=CC=CC=1.CCCCCCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]2[N:9]([CH3:16])[C:10]([C:11]([F:12])([F:13])[F:14])=[CH:24][C:7]=2[C:21]#[N:22])=[CH:17][CH:18]=1

Participants

6

Reactant 3

HCID 8857Ethyl Acetate2×HCID 701982-ChloroacrylonitrileHCID 15430850HCID 15430850, compound

Product 1

HCID 118221892-(4-chlorophenyl)-1-methyl-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrileYield 22%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8900HeptaneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of N-(p-chloro-α-cyanobenzyl)-2,2,2-trifluoro-N-methylacetamide (13.8 g, 0.05 mol) in toluene is treated with tetrafluoroboric acid-diethyl etherate (10.5 g as is, 8.9 g real, 0.055 mol) at room temperature, heated to 60° C., treated with 2-chloroacrylonitrile (6.9 g, 0.075 mol) over a 25 minute period, held for 2 to 2.5 hours at 60° C., cooled and treated with ethyl acetate. The resultant solution is washed with water and concentrated to give a waxy residue. Flash column chromatography of the residue on silica gel packed with 15% ethyl acetate in heptane and eluted with 20% ethyl acetate in heptane gives the title product as pale yellow crystals, 3.1 g (22% yield), mp 129°-130° C., identified by 1H, 13C, and 19F NMR analyses.

Workup

  1. temperaturecooled
  2. washThe resultant solution is washed with water
  3. concentrationconcentrated
  4. customto give a waxy residue
  5. washeluted with 20% ethyl acetate in heptane

Sources & evidence

ORD record
ord-a8e9372ce2804772b33e2de6daf06466
Source dataset
uspto-grants-1998_05
Patent number
US05750726

Reaction notes

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