Tetrahydrofuran → Lithium 3-fluoropyridine-2-carboxylate

温度

-75 °C

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.

1. temperaturecooled to −70° C. to −60° C
2. temperatureTemperature of the reaction mixture (RM) was maintained at −70° C. to −60° C. for 1 hour
3. temperaturewhile maintaining the temperature in the range of −75° C. to −70° C
4. stirringThe RM was stirred at the same temperature for 4 hours
5. temperaturecooled to −70° C.
6. customby bubbling of CO2 gas for 1 hour
7. additionwas added dropwise using cannula
8. temperaturemaintaining the reaction temperature below −70° C. (−70° C. to −60° C.)
9. customBubbling of CO2 gas
10. waitwas continued for another hour
11. customwas slowly brought to +30° C
12. filtrationThe resulting solid was filtered
13. customdried
14. washwashed with 100 mL of 1:1 THF
15. dry with materialMTBE, then vacuum dried at 45° C.

ORDレコード

ord-83abc0fdad714a4098da53e923952f2d

出典データセット

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08541580B2