Toluene → HCID 86623338, compound

HRID 383731Notes

Reaction equation

HRID 383731 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH3:13])=[CH:11][C:10]([C:14](O)=[O:15])=[C:9]2[CH3:17])=[C:4]([C:18]([F:21])([F:20])[F:19])[CH:3]=1.C1(C)C=CC=CC=1.S(Cl)([Cl:31])=O>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH3:13])=[CH:11][C:10]([C:14]([Cl:31])=[O:15])=[C:9]2[CH3:17])=[C:4]([C:18]([F:21])([F:20])[F:19])[CH:3]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 24386Thionyl ChlorideHCID 67011838HCID 67011838, compound

Product 1

HCID 86623338HCID 86623338, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
1.5 °C

Procedure

To a solution of 1-[4-fluoro-2-(trifluoromethyl)phenyl]-2,5-dimethyl-1H-pyrrole-3-carbaldehyde (1.5 g, 5.3 mmol) in acetone (150 mL) was added a 0.3 M solution of KMnO4 (150 mL). The reaction mixture was stirred 3 h at room temperature and then was charged with 10% H2O2 (5 mL). After 15 minutes the reaction mixture was filtered and the filtrate was concentrated in vacuo to remove acetone. The remaining aqueous suspension was acidified with acetic acid. The precipitates were recovered by filtration and dried under high vacuum to afford 1-(4-fluoro-2-(trifluoromethyl)phenyl]-2,5-dimethyl-1H-pyrrole-3-carboxylic acid (0.99 g, 62%) as a faintly yellow powder; 1H NMR (CDCl3): δ 7.56 (dd, J=8, 3 Hz, 1H), 7.41 (m, 1H), 7.27 (dd, J=5, 8 Hz, 1H), 6.42 (s, 1H), 2.21 (s, 3H), 1.90 (s, 3H); MS (ESI) m/z 302 [M+H]+. To a suspension of 1-(4-fluoro-2-(trifluoromethyl)phenyl]-2,5-dimethyl-1H-pyrrole-3-carboxylic acid (0.65 g, 2.16 mmol) in anhyd toluene (5.0 mL) cooled to 0-3° C. were added thionyl chloride (0.25 mL) and DMF (20 μL). The reaction mixture was allowed to warm to room temperature where it remained for 3 h and then was concentrated in vacuo. The residue was evaporated twice from 5 mL of toluene to remove thionyl chloride and then was triturated in 3 mL of hexanes. The solids were removed by filtration and the filtrate was concentrated under reduced pressure and dried under high vacuum to afford the title compound (0.44 g, 64%) as a pale brown solid; 1H NMR (CDCl3): δ 7.59 (dd, J=8, 3 Hz, 1H), 7.44 (m, 1H), 7.27 (dd, J=5, 8 Hz, 1H), 6.51 (s, 1H), 2.17 (s, 3H), 1.89 (s, 3H); MS (ESI) m/z 320 [M+H]+.

Workup

  1. temperatureto warm to room temperature where it
  2. concentrationwas concentrated in vacuo
  3. customThe residue was evaporated twice from 5 mL of toluene
  4. customto remove thionyl chloride
  5. customwas triturated in 3 mL of hexanes
  6. customThe solids were removed by filtration
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-2e7db6fe2dbc466e8c0c52a75998dfcb
Source dataset
uspto-grants-2013_02
Patent number
US08367667B2

Reaction notes

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