Nicotinic Acid → 6-tert-Butylpyridine-3-carboxylic acid

HRID 2199783Notes

Reaction equation

HRID 2199783 reaction equation
[C:1]([OH:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.S(=O)(=O)(O)O.[C:15](O)(=O)[C:16](C)([CH3:18])[CH3:17].S(OOS([O-])(=O)=O)([O-])(=O)=O.[NH4+].[NH4+]>O.[Al].[N+]([O-])([O-])=O.[Ag+]>[C:16]([C:5]1[CH:6]=[CH:7][C:2]([C:1]([OH:9])=[O:8])=[CH:3][N:4]=1)([CH3:18])([CH3:17])[CH3:15]

Participants

8

Reactant 4

HCID 938Nicotinic AcidHCID 1118Sulfuric AcidHCID 6417Pivalic acidHCID 62648Ammonium Persulfate

Product 1

HCID 218978046-tert-Butylpyridine-3-carboxylic acidYield 4.8%

Reagents, catalysts & solvents 3

HCID 24470Silver NitrateCatalystHCID 962WaterSolventHCID 5359268AluminumSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of nicotinic acid (2.00 g, 16.2 mmol) in water (250 mL) was added concentrated sulfuric acid (1 mL, 18.8 mmol) and the mixture stirred under nitrogen to form a clear solution. Pivalic acid (1.83 g, 17.9 mmol) was added and stirring under nitrogen at ambient temperature continued for 10 minutes. Silver nitrate (125 mg, 0.74 mmol) was added followed by ammonium persulfate (295 mg, 1.3 mmol), the flask wrapped in aluminum foil to exclude light and the mixture heated to 90° C. under nitrogen. After 2 hours the reaction mixture was cooled to ambient temperature and the aqueous mixture concentrated in vacuo to a colorless solid. The solid was triturated with tetrahydrofuran and filtered. The solid residue was retriturated with methanol and filtered. Both filtrates were combined and concentrated in vacuo. The crude product was purified by reverse phase chromatography using a 85 g C-18 column gradient eluted from 10% acetonitrile in water to 100% acetonitrile. The product containing fractions were combined and concentrated in vacuo. The residue was lyophilized from water to give 6-tert-butylnicotinic acid as a colorless solid (139 mg, 4%).

Workup

  1. customto form a clear solution
  2. stirringstirring under nitrogen at ambient temperature
  3. temperatureAfter 2 hours the reaction mixture was cooled to ambient temperature
  4. concentrationthe aqueous mixture concentrated in vacuo to a colorless solid
  5. customThe solid was triturated with tetrahydrofuran
  6. filtrationfiltered
  7. customThe solid residue was retriturated with methanol
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by reverse phase chromatography
  11. washeluted from 10% acetonitrile in water to 100% acetonitrile
  12. additionThe product containing fractions
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-629265330be84d1d99ccbb27c5c46353
Source dataset
uspto-grants-2016_06
Patent number
US09359345B2

Reaction notes

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