Tetrahydrofuran → Lithium 3-fluoropyridine-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

240 mL of Methyl t-butyl ether (MTBE) and 18.55 mL of N,N,N′,N′-tetramethylethylenediamine (TMEDA) are taken in a reaction flask under nitrogen atmosphere and cooled to −70° C. to −60° C. To the cooled mass, 80 mL of n-BuLi (1.6 M in hexane) was added dropwise with stirring. Temperature of the reaction mixture (RM) was maintained at −70° C. to −60° C. for 1 hour. The RM was cooled to −75° C., then 10 g of 3-fluoropyridine (in 10 mL of MTBE) was added dropwise while maintaining the temperature in the range of −75° C. to −70° C. The RM was stirred at the same temperature for 4 hours. Meanwhile, in another reaction flask, 100 mL of tetrahydrofuran (THF) was taken and cooled to −70° C. followed by bubbling of CO2 gas for 1 hour. To this solution, lithiated 3-fluoropyridine solution (mixture of 3-fluoropyridine+n-BuLi+TMEDA in MTBE) was added dropwise using cannula maintaining the reaction temperature below −70° C. (−70° C. to −60° C.). Bubbling of CO2 gas was continued for another hour and then the reaction temperature was slowly brought to +30° C. The resulting solid was filtered, dried and washed with 100 mL of 1:1 THF:MTBE, then vacuum dried at 45° C., resulting in 14.5 g of the titled compound.

Provenance & Evidence