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 12.1, 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 placed in a 25 ml sealed tube equipped with a magnetic stirrer and maintained under an argon sparge. After a few minutes, 0.05 g (0.22 mmol) of palladium acetate is added. The reaction mixture is stirred for 20 minutes while sparging with argon and is then rapidly sealed and maintained at 100° C. for 2 hours 30 minutes. The cooled solution is concentrated to dryness under reduced pressure. The residue is then taken up in ethyl acetate (100 ml) and water (75 ml). The organic phase is washed with water and then extracted with twice 50 ml of aqueous 2N sodium hydroxide solution. 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 sulfate 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