Carbon Dioxide → 2,6-Difluoropyridine-3-carboxylic acid

HRID 1367295Notes

Reaction equation

HRID 1367295 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[N:3]=1.C([Li])CCC.[C:14](=[O:16])=[O:15].O>O1CCCC1>[F:8][C:4]1[N:3]=[C:2]([F:1])[CH:7]=[CH:6][C:5]=1[C:14]([OH:16])=[O:15]

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 962WaterHCID 739342,6-DifluoropyridineHCID 178418339Butyllithium

Product 1

HCID 105830702,6-Difluoropyridine-3-carboxylic acidYield 57.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 2,6-difluoropyridine (58, 7.10 g, 0.0617 mol) in tetrahydrofuran (150.0 mL) under an atmosphere of nitrogen at −78° C., n-butyllithium (26.0 mL, 2.50 M in hexane) was added slowly. After 30 minutes, dry ice (3.0 g) was added to the reaction. After 1 hour, the reaction was allowed to warm to room temperature, then poured into water and extracted with ethyl acetate. The aqueous layer was acidified with 1 N HCl to pH =4-5 and extracted with ethyl acetate. The organic layer was dried over anyhydrous sodium sulfate, filtered and concentrated to give the crude compound as a light yellow solid (59, 5.6 g, 57.0%).

Workup

  1. waitAfter 1 hour
  2. extractionextracted with ethyl acetate
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over anyhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-22c17db2c05e440f9c7715a1e2188bf9
Source dataset
uspto-grants-2011_02
Patent number
US07893075B2

Reaction notes

Loading…