Carbon Dioxide → 2-Fluoro-5-methoxynicotinic acid

HRID 1409498

Reaction equation

HRID 1409498 reaction equation
[Li]CCCC.[F:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][N:8]=1.[C:15](=[O:17])=[O:16].O>C1COCC1>[F:6][C:7]1[N:8]=[CH:9][C:10]([O:13][CH3:14])=[CH:11][C:12]=1[C:15]([OH:17])=[O:16]

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 962WaterHCID 189731092-Fluoro-5-methoxypyridineHCID 178418339Butyllithium

Product 1

HCID 667280732-Fluoro-5-methoxynicotinic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-55f725c0e0be43fdb8db2f50118dd163
Source dataset
uspto-grants-2014_12
Patent number
US08921363B2

Linked notes

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