Dimethylformamide → Methyl 2-(p-chlorophenyl)-5-(trifluoromethyl)pyrrole-3-carboxylate

HRID 1955985Notes

Reaction equation

HRID 1955985 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#N)=[CH:4][CH:3]=1.FC(F)(F)S(O)(=O)=O.CN(C)C=O.Cl[C:32](=[CH2:37])[C:33]([O:35][CH3:36])=[O:34]>C1(C)C=CC=CC=1.O.C(OCC)(=O)C>[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:37][C:32]=2[C:33]([O:35][CH3:36])=[O:34])=[CH:16][CH:17]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 6659Methyl 2-chloroacrylateHCID 62406Trifluoromethanesulfonic acidHCID 9903361N-(p-chloro-a-cyanobenzyl)-2,2,2-trifluoroacetamide

Product 1

HCID 11034029Methyl 2-(p-chlorophenyl)-5-(trifluoromethyl)pyrrole-3-carboxylateYield 62%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A slurry of N-(p-chloro-α-cyanobenzyl)-2,2,2-trifluoroacetamide (10.5 g, 0.04 mol) in toluene under a nitrogen atmosphere is cooled to 10° C., treated with trifluoromethanesulfonic acid (12.0 g, 0.08 mol) over 10-15 minutes, allowed to warm to room temperature and stirred for 3 hours. The reaction is monitored by 19F NMR (DMSO-d6) analysis to show completion of the intermediate salt formation. When formation is complete, the mixture is cooled to 10° C., treated with dimethylformamide, treated with methyl 2-chloroacrylate (7.2 g, 0.06 mol), allowed to warm to room temperature, stirred for 18 hours, and diluted with water and ethyl acetate. The phases are separated and the organic phase is washed with water and concentrated to give a waxy solid residue. Flash column chromatography of the residue on silica gel, packed and eluted with 20% ethyl acetate in heptane gives the title product as a white crystalline solid, 7.6 g (62% yield), mp 123°-125° C. identified by 1H and 19F NMR analyses.

Workup

  1. temperaturethe mixture is cooled to 10° C.
  2. temperatureto warm to room temperature
  3. stirringstirred for 18 hours
  4. customThe phases are separated
  5. washthe organic phase is washed with water
  6. concentrationconcentrated
  7. customto give a waxy solid residue
  8. washeluted with 20% ethyl acetate in heptane

Sources & evidence

ORD record
ord-0147ab6fec6c4ae6b27fc1ff59ac1782
Source dataset
uspto-grants-1998_07
Patent number
US05777132

Reaction notes

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