Hydrochloric Acid → 1-Methyl-5-p-toluoylpyrrole 2-acetamidoacetic acid ethyl ester

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Reaction Steps

A solution of 3.4 grams (0.021 moles) of 1,1'-carbonyldiimidazole in 70 ml of anhydrous tetrahydrofuran was added under vigorous stirring and cooling on iced water in such a way as to maintain the temperature at about 20° C. to a solution of 4.6 grams (0.018 moles) of 1-methyl-5-p-toluoylpyrrole-2-acetic acid in 150 ml of anhydrous tetrahydrofuran (THF). The addition lasted about 30 minutes. Subsequently, the resulting mixture was left under vigorous stirring at 20° C. for 1 hour. Then to the mixture 3.2 grams (0.023 moles) of aminoacetic acid ethyl ester hydrochloride were added and the resulting suspension was kept under vigorous stirring while 3.2 ml (2.3 grams; 0.023 moles) of triethylamine dissolved in 20 ml of anhydrous THF were added dropwise to the suspension (the addition of this reactant can be omitted in those cases wherein the free amine is used in lieu of its hydrochloride). The mixture was kept under stirring at 20° C. for 3 hours, then the triethylamine hydrochloride which precipitated was filtered off and the clear solution thus obtained was evaporated under reduced pressure on a water bath at 55° C. The thick and oily residue which formed was dissolved in 200 ml of ethyl acetate and transferred into a separatory funnel. The organic solution was first washed with 1N NaOH (3×30 ml) in order to remove the unreacted 1-methyl-5-p-toluoylpyrrole-2-acetic acid, then with water (3×30 ml). Subsequently, the washings were continued with 1N HCl (3×30 ml) in order to remove the excess starting amine which did not react, and finally the organic solution was washed with a saturated solution of NaCl (3×30 ml) until neutrality was reached. The organic solution was dried by letting it stand for 12 hours on anhydrous sodium sulphate. After filtration the solvent was removed by evaporation under vacuum on a water bath at 50° C. A solid residue was thus obtained which, after crystallization from benzene-cyclohexane (1:1), gave 4.8 grams of a compound of formula: ##STR22## having the following chemico-physical characteristics: Formula: C19H22N2O4.

Provenance & Evidence