Hydrogen Peroxide → Ketorolac methyl ester

HRID 53900

Reaction equation

HRID 53900 reaction equation
[CH3:1][O:2][C:3](=[O:21])[CH:4](I)[CH2:5][CH2:6][N:7]1[CH:11]=[CH:10][CH:9]=[C:8]1[C:12](=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.OO>CS(C)=O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Fe+2]>[CH3:1][O:2][C:3]([CH:4]1[CH2:5][CH2:6][N:7]2[C:8]([C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[CH:9][CH:10]=[C:11]12)=[O:21]

Participants

5

Reactant 2

HCID 784Hydrogen PeroxideHCID 540699414-(2-Benzoylpyrrol-1-yl)-2-iodobutyric acid methyl ester

Product 1

HCID 9921553Ketorolac methyl ester

Reagents, catalysts & solvents 2

HCID 62662Ferrous sulfate heptahydrateCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

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.

Sources & evidence

ORD record
ord-23fb02806af240b7bf87cb4f592c23d5
Source dataset
uspto-grants-1997_04
Patent number
US05621115

Linked notes

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