Carbon Dioxide → 2-Fluoro-5-methoxynicotinic acid

温度

-70 °C

To a solution of DIPA (54.0 mL, 385 mmol) in THF (1101 mL, 385 mmol) at −60° C. was added BuLi, 2.5 M in hexanes (154 mL, 385 mmol) over 5 minutes such that the internal temperature was maintained below −60° C. After stirring for 45 minutes at −65° C. a solution of 2-fluoro-5-methoxypyridine (49 g, 385 mmol) in 200 mL of THF was added over the course of 2 minutes maintaining an internal temperature <−65° C. The reaction was stirred at −70° C. for 1.5 hours then reaction was poured into a 3 L flask containing 1200 g of crushed dry ice. The reaction was allowed to warm to 0° C. and then poured into 1000 mL of water. The organics were removed under reduced pressure and the aqueuous layer was acidified with 1100 mL of 2 N HCl. The resulting thick white slurry was stirred for 1 hour then filtered to provide 2-fluoro-5-methoxynicotinic acid as a white solid.

1. temperaturewas maintained below −60° C
2. additionwas added over the course of 2 minutes
3. temperaturemaintaining an internal temperature <−65° C
4. customreaction
5. additionwas poured into a 3 L flask
6. temperatureto warm to 0° C.
7. customThe organics were removed under reduced pressure
8. stirringThe resulting thick white slurry was stirred for 1 hour
9. filtrationthen filtered

ORDレコード

ord-67f4545bf8534911b6399b73e7339bf4

出典データセット

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08883782B2