Carbon Dioxide → 2-Fluoro-6-phenylpyridine-3-carboxylic acid

HRID 915640Notes

Reaction equation

HRID 915640 reaction equation
[Li+].CC([N-]C(C)C)C.[F:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:11]=1.[C:22](=[O:24])=[O:23].Cl>O1CCCC1>[F:9][C:10]1[C:15]([C:22]([OH:24])=[O:23])=[CH:14][CH:13]=[C:12]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:11]=1

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 313Hydrochloric AcidHCID 2724682Lithium diisopropylamide2×HCID 27628912-fluoro-6-phenylpyridine

Product 1

HCID 463149432-Fluoro-6-phenylpyridine-3-carboxylic acidYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Cool a solution of LDA (3.46 mmol) in anhydrous tetrahydrofuran (6 mL) to −78° C. Cannulate the 2-fluoro-6-phenylpyridine in anhydrous tetrahydrofuran (6 mL) to the cooled LDA solution. Stir at −78° C. for 30 minutes then bubble carbon dioxide gas through the solution for 10 minutes. Allow the reaction to come to room temperature and purge with argon. Extract the reaction with 1M sodium hydroxide and discard the organics. Acidify the aqueous layer with conc. HCl and extract with ethyl acetate. Dry the organic layer over magnesium sulfate, filter and evaporate to yield the title compound as a light yellow solid (405 mg, 65%). MS (m/e): 216.1 (M−).

Workup

  1. customAllow the reaction
  2. customto come to room temperature
  3. custompurge with argon
  4. extractionExtract
  5. customthe reaction with 1M sodium hydroxide
  6. extractionextract with ethyl acetate
  7. dry with materialDry the organic layer over magnesium sulfate
  8. filtrationfilter
  9. customevaporate

Sources & evidence

ORD record
ord-71ddd30b4a69480a9aa869e6c118405f
Source dataset
uspto-grants-2007_09
Patent number
US07265246B2

Reaction notes

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