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

HRID 2224730Notes

Reaction equation

HRID 2224730 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>C1COCC1>[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 THF (6 mL) to −78° C. Cannulate the 2-fluoro-6-phenylpyridine in anhydrous THF (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 1 M NaOH and discard the organics. Acidify the aqueous layer with conc. HCl and extract with ethyl acetate. Dry the organic layer over MgSO4, filter and evaporate to yield the title compound as a light yellow solid (405 mg, 65%). MS (ES): m/z 216.1 (M−H).

Workup

  1. customAllow the reaction
  2. customto come to room temperature
  3. custompurge with argon
  4. extractionExtract
  5. customthe reaction with 1 M NaOH
  6. extractionextract with ethyl acetate
  7. dry with materialDry the organic layer over MgSO4
  8. filtrationfilter
  9. customevaporate

Sources & evidence

ORD record
ord-fbfab1f7e2b641bfb8d004d0bc684f19
Source dataset
uspto-grants-2008_05
Patent number
US07378447B2

Reaction notes

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