Hydrogen Peroxide → Ketorolac methyl ester

Participants

Reaction Steps

As set out in Scheme 1, 2-benzoylpyrrole (II, prepared according to known procedures, e.g., J. Org. Chem. 1977, 42, 4248) is N-alkylated in step 1 with gamma-butyrolactone to provide, after esterification, 4-(2-benzoylpyrrol-1-yl)butyric acid methyl ester (III). 4-(2-Benzoylpyrrol-1-yl)butyric acid methyl ester (III) is then iodinated in step 2 with lithium diisopropylamide and a source of electrophilic iodine, such as iodine, iodine monochloride, or N-iodosuccinimide, to yield 4-(2-benzoylpyrrol-1-yl)-2-iodobutyric acid methyl ester (IV). 4-(2-Benzoylpyrrol-1-yl)-2-iodobutyric acid methyl ester (IV) is then cyclized in step 3 via a free radical ring closure reaction, for example, with hydrogen peroxide and iron (II) sulfate heptahydrate in dimethylsulfoxide, to yield 5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid methyl ester (V). 5-Benzoyl-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid methyl ester (V) is then hydrolyzed in step 4 to the corresponding acid (I, ketorolac) by known procedures, e.g., U.S. Pat. No. 4,089,969.

Provenance & Evidence