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

HRID 2256172Notes

Reaction equation

HRID 2256172 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[N:3]=1.C([N-]C(C)C)(C)C.[Li+].[C:17](=[O:19])=[O:18]>C1CCCCC1.C1COCC1.O>[F:8][C:4]1[N:3]=[C:2]([F:1])[CH:7]=[CH:6][C:5]=1[C:17]([OH:19])=[O:18]

Participants

7

Reactant 3

HCID 280Carbon DioxideHCID 739342,6-DifluoropyridineHCID 2724682Lithium diisopropylamide

Product 1

HCID 105830702,6-Difluoropyridine-3-carboxylic acidYield 97%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8078CyclohexaneSolvent

Procedure

2,6-Difluoropyridine (7.89 mL, 0.087 mmol) is added dropwise under N2 at 78° C. to a stirred solution of lithium diisopropylamide (59.0 mL of a 1.5N solution in cyclohexane, 0.089 mmol) in THF (250 mL). After 2 h at 78° C., a stream of dry CO2 is passed through the solution and the mixture is diluted with water and washed with EtOAc. The aqueous portion is neutralized with 3N HCl, extracted with EtOAc and worked up to give 2,6-difluoronicotinic acid (13.4 g, 97%). 1H NMR (DMSO) δ 8.59 (1H, dd, J=9.2, 8.2 Hz), 7.30 (1H, dd, J=8.2, 2.1 Hz), 4.03 (1H, brs).

Workup

  1. washwashed with EtOAc
  2. extractionextracted with EtOAc

Sources & evidence

ORD record
ord-3f2b791c3c51468dad1c3ece1943ff8c
Source dataset
uspto-grants-1997_08
Patent number
US05654307

Reaction notes

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