Pyruvic Acid → 5-Fluoro-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

0.5 g (2.10 mmol) of 2-amino-3-iodo-5-fluoropyridine obtained in step 5.1, 0.55 g (6.3 mmol) of pyruvic acid, 0.71 g (6.3 mmol) of 1,4-diazabicyclo[2.2.2]octane (DABCO) and 15 ml of anhydrous dimethylformamide are introduced into a 25 ml sealed tube equipped with a magnetic stirrer and subjected to sparging with argon. After a few minutes, 0.05 g (0.22 mmol) of palladium acetate is added. The reaction mixture is kept stirring and subjected to sparging with argon for 20 minutes and then rapidly sealed and brought to 100° C. for 2 h 30. The cooled solution is concentrated under reduced pressure. The residue is subsequently taken up with ethyl acetate (100 ml) and water (75 ml). The organic phase is washed with water and then extracted with twice 50 ml of a 2N aqueous solution of sodium hydroxide. The basic aqueous phases are combined, cooled to 0° C. and then acidified by adding hydrochloric acid (pH 3). The medium is extracted with ethyl acetate (4×50 ml), and the combined organic phases are dried over sodium sulphate and then concentrated under reduced pressure. 0.158 g (0.88 mmol) of the expected product is obtained in the form of a yellow powder.

Provenance & Evidence