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

HRID 1396152Notes

Reaction equation

HRID 1396152 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

In a round bottom flask, to 2,6-difluoro-pyridine (39, 7.10 g, 61.7 mmol) in 150.0 mL of tetrahydrofuran under an atmosphere of nitrogen at −78° C., n-butyllithium (26.0 mL, 2.50 M in hexane, 65.0 mmol) is slowly added. After 30 minutes, 3.0 g of dry ice is added and an hour later the reaction is allowed to warm to room temperature. The reaction is poured into water, extracted with ethyl acetate and the aqueous layer is adjusted to pH 4-5 with 1 N hydrochloric acid. This is extracted with ethyl acetate and the organic layer is dried over sodium sulfate, filtered and the filtrate concentrated under vacuum to provide the desired compound (51, 5.6 g).

Workup

  1. extractionextracted with ethyl acetate
  2. extractionThis is extracted with ethyl acetate
  3. dry with materialthe organic layer is dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under vacuum

Sources & evidence

ORD record
ord-c3f3ae25133d4913b5ce3d2db23d96fa
Source dataset
uspto-grants-2014_12
Patent number
US08901118B2

Reaction notes

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