Formic Acid → Methyl 5-fluoro-6-(pyrrolidin-1-yl)nicotinate

Participants

Reaction Conditions

Reaction Steps

To a solution of 1.7 g of methyl 2-chloro-5-fluoro-6-(pyrrolidin-1-yl)nicotinate in 15 mL of N,N-dimethylformamide, 0.38 g of tetrakis(triphenylphosphine)palladium(0) and 1.4 mL of triethylamine were added at room temperature, and 0.37 mL of formic acid was dropped thereto. The mixture was stirred at 80 to 90° C. for 2 hours 30 minutes under a nitrogen atmosphere. After cooling to room temperature, water and ethyl acetate were added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, and the resultant solution was washed with a saturated aqueous sodium chloride solution. To the organic layer, a mixed solvent of chloroform:methanol was added, the organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. To the resultant residue, a mixed solvent of diethyl ether:ethyl acetate (1:2) was added, the insoluble substance was filtered off, and the solvent was distilled off under reduced pressure. The resultant residue was purified by flash silica gel column chromatography using an eluent of chloroform to obtain 1.3 g of methyl 5-fluoro-6-(pyrrolidin-1-yl)nicotinate as a light yellow solid.

Provenance & Evidence