Methyl iodide → 1-methyl-4-(trifluoromethyl)-1H-pyrrole-3-carboxylic acid

HRID 2214338Notes

Reaction equation

HRID 2214338 reaction equation
[H-].[Na+].[F:3][C:4]([F:13])([F:12])/[CH:5]=[CH:6]/[C:7]([O:9]CC)=[O:8].CC1C=CC(S([CH2:24][N+:25]#[C-:26])(=O)=O)=CC=1.[CH3:27]I>CS(C)=O.C(OCC)C.C(O)C.[OH-].[Na+]>[CH3:24][N:25]1[CH:26]=[C:5]([C:4]([F:13])([F:12])[F:3])[C:6]([C:7]([OH:9])=[O:8])=[CH:27]1

Participants

9

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 161915Tosylmethyl isocyanideHCID 5371261Ethyl (2E)-4,4,4-trifluoro-2-butenoate

Product 1

HCID 117887791-methyl-4-(trifluoromethyl)-1H-pyrrole-3-carboxylic acid

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolvent2×HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 14798Sodium HydroxideSolvent

Procedure

Sodium hydride (8.0 g of a 75% dispersion in oil) is suspended at +5° C. in a mixture of DMSO (300 ml) and diethylether (100 ml). A solution of ethyl 4,4,4-trifluorocrotonate (20 g) and TOSMIC (23 g) in DMSO (100 ml) is added through a dropping funnel at such a rate that the temperature does not exceed 10° C. After stirring the reaction mixture for an additional hour at room temperature methyl iodide (15.6 ml) is added with cooling. After 2 hours at room temperature the reaction mixture is poured onto crushed ice. Repeated extraction with ether, washing of the combined organic phases with brine and evaporation of the solvent under reduced pressure gives a product mixture in form of a light amber oil. The crude product mixture is heated at 60° C. in a mixture of ethanol (100 ml) and sodium hydroxide (50 ml of a 30% aqueous solution). Washing of the solution with ether, acidifying of the aqueous phase with concentrated hydrochloric acid and filtering gives the 1-methyl-4-trifluoromethylpyrrole-3-carboxylic acid in form of a crystalline solid. 1H-NMR (CDCl3): 7.24(d,1H); 6.88(d,1H); 3.63(s,3H).

Workup

  1. customdoes not exceed 10° C
  2. additionis added
  3. temperaturewith cooling
  4. additionAfter 2 hours at room temperature the reaction mixture is poured
  5. customonto crushed ice
  6. extractionextraction with ether
  7. washwashing of the combined organic phases with brine and evaporation of the solvent under reduced pressure
  8. customgives a product mixture in form of a light amber oil
  9. washWashing of the solution with ether, acidifying of the aqueous phase with concentrated hydrochloric acid
  10. filtrationfiltering

Sources & evidence

ORD record
ord-b39ea812b11648f5a0c59b69b7f8365d
Source dataset
uspto-grants-2006_09
Patent number
US07109150B2

Reaction notes

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