Reaction #75466

Reaction equation

trifluorocrotonate

TOSMIC

Sodium hydride

methyl iodide

→

1-methyl4-trifluoromethylpyrrole-3-carboxylic acid

Solvents

DMSO

ethanol

sodium hydroxide

DMSO

diethylether

Conditions

Workup

1. 1
   Otherdoes not exceed 10° C
2. 2
   workup.ADDITIONis added
3. 3
   Temperaturewith cooling
4. 4
   workup.ADDITIONAfter 2 hours at room temperature the reaction mixture is poured
5. 5
   Otheronto crushed ice
6. 6
   Extractionextraction with ether
7. 7
   Washwashing of the combined organic phases with brine and evaporation of the solvent under reduced pressure
8. 8
   Othergives a product mixture in form of a light amber oil
9. 9
   WashWashing of the solution with ether, acidifying of the aqueous phase with concentrated hydrochloric acid
10. 10
    Filtrationfiltering

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, 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 (15.8 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-methyl4-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).

Source