Pyrrole → 5-[(4-chlorophenyl)(methylimino)methyl]-4-methyl-1H-pyrrole-2-acetic acid

HRID 370927Notes

Reaction equation

HRID 370927 reaction equation
[CH3:1][N:2]=[C:3](Cl)[C:4]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][CH:5]=1.ClS(O)(=O)=O.[CH3:17][C:18]1[CH:19]=[C:20]([CH2:23][C:24]([O:26]CC)=[O:25])[NH:21][CH:22]=1.N1C=CC=C1.Cl(O)(=O)(=O)=O>CCOCC>[Cl:10][C:7]1[CH:8]=[CH:9][C:4]([C:3](=[N:2][CH3:1])[C:22]2[NH:21][C:20]([CH2:23][C:24]([OH:26])=[O:25])=[CH:19][C:18]=2[CH3:17])=[CH:5][CH:6]=1

Participants

7

Reactant 5

HCID 8027PyrroleHCID 24247Perchloric AcidHCID 24638Chlorosulfonic acidHCID 12341506N-Methyl 4-Chlorobenzimidoyl ChlorideHCID 13130821Ethyl (4-methyl-1H-pyrrol-2-yl)acetate

Product 1

HCID 1359873645-[(4-chlorophenyl)(methylimino)methyl]-4-methyl-1H-pyrrole-2-acetic acidYield 12.8%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

N-Methyl 4-chlorobenzimidoyl chloride (2.37 g, 12.6 mmole) was placed in a dry 50 ml round bottom flask and treated with alcohol free chloroform and chlorosulfonic acid (0.15 g, 1.3 mmole). The reaction was placed under a nitrogen atmosphere and stirred at room temperature while ethyl 4-methyl-1H-pyrrole-2-acetate (2.11 g, 12.6 mmole) was added dropwise over a five-minute period. Upon addition of the pyrrole, the reaction mixture turned dark brown and the reaction temperature rose. The reaction was stirred overnight at room temperature, then quenched with saturated aqueous sodium bicarbonate. The phases were separated and the organic phase was extracted with saturated aqueous sodium bicarbonate, washed with water, dried over sodium sulfate, filtered, and concentrated. The residue was dissolved in absolute ethanol, treated with 70% perchloric acid (2.0 g, 14 mmole) cooled and diluted with ether. A brown viscous liquid separated which was suspended in methylene chloride and treated with saturated aqueous sodium bicarbonate. The solution was dried over sodium sulfate, filtered, and concentrated. The residue was placed on a silica gel column and eluted with methylene chloride/methanol (99/1) to remove nonpolar impurities. The silica gel was extracted with methanol to yield 0.47 g (12%) of the title compound as a dark brown solid, m.p. 79°-80° C. (dec).

Workup

  1. additionwas added dropwise over a five-minute period
  2. customquenched with saturated aqueous sodium bicarbonate
  3. customThe phases were separated
  4. extractionthe organic phase was extracted with saturated aqueous sodium bicarbonate
  5. washwashed with water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe residue was dissolved in absolute ethanol
  10. temperaturecooled
  11. customA brown viscous liquid separated which
  12. additiontreated with saturated aqueous sodium bicarbonate
  13. dry with materialThe solution was dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated
  16. washeluted with methylene chloride/methanol (99/1)
  17. customto remove nonpolar impurities
  18. extractionThe silica gel was extracted with methanol

Sources & evidence

ORD record
ord-06311066ae1e467e862b145e0b0c0ad4
Source dataset
uspto-grants-1985_07
Patent number
US04528382

Reaction notes

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