Carbon Dioxide → 3-Fluoropyridine-2-carboxylic acid

HRID 925263Notes

Reaction equation

HRID 925263 reaction equation
N12CCN(CC1)CC2.C([Li])CCC.[F:14][C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1.[C:21](=[O:23])=[O:22]>C(OCC)C>[F:14][C:15]1[C:16]([C:21]([OH:23])=[O:22])=[N:17][CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 9237DabcoHCID 677943-FluoropyridineHCID 178418339Butyllithium

Product 1

HCID 27627863-Fluoropyridine-2-carboxylic acidYield 83%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a solution of 1,4-diazabicyclo[2.2.2]octane (1.15 g, 10.3 mmol) in diethylether (50 ml) is added n-butyllithium (2.6M in hexane) (3.95 ml, 10.3 mmol) at −78° C. The reaction mixture is stirred at −20° C. for 1 h followed by the addition of a solution of 3-fluoro-pyridine (1.00 g, 10.29 mmol) in diethylether (30 ml) at −78° C. The yellow suspension is stirred at −60° C. for 1 h and then cooled to −78° C. followed by the addition of excess dry ice. The resulting solution allowed to warm to to −10° C. over 20 min. The precipitate is filtered and the residue is washed with ether which yields pure 3-fluoro-pyridine-2-carboxylic acid (1.20 g, 8.51 mmol, 83%).

Workup

  1. stirringThe yellow suspension is stirred at −60° C. for 1 h
  2. temperaturecooled to −78° C.
  3. temperatureto warm to to −10° C. over 20 min
  4. filtrationThe precipitate is filtered
  5. washthe residue is washed with ether which

Sources & evidence

ORD record
ord-a592cda8bdcf432f98ca0a01571afb29
Source dataset
uspto-grants-2016_03
Patent number
US09284286B2

Reaction notes

Loading…