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

HRID 551878Notes

Reaction equation

[C:1]([OH:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.[C:10](C(O)=O)([CH3:13])([CH3:12])[CH3:11].S(OOS([O-])(=O)=O)([O-])(=O)=O.[NH4+].[NH4+]>O.OS(O)(=O)=O.[Al].[N+]([O-])([O-])=O.[Ag+]>[C:10]([C:5]1[CH:6]=[CH:7][C:2]([C:1]([OH:9])=[O:8])=[CH:3][N:4]=1)([CH3:13])([CH3:12])[CH3:11]

Participants

Conditions

Temperature: 90 °C

Procedure

Nicotinic acid (1.0 g; 7.3 mmol) is dissolved in a mixture of water (10 mL) and conc. H2SO4 (0.5 mL) with stirring. tert-Butyl carboxylic acid is added, and the resulting crystalline slurry stirred under nitrogen. Catalytic AgNO3 and ammonium persulfate (140 mg; 0.61 mmol) are then added, the flask wrapped in aluminum foil to shield from light and the reaction heated to 90° C. for 3 hr. The reaction is cooled to 0° C., basified to pH 10 and extracted with EtOAc (4×50 mL). The pooled organic layers are washed with saturated sodium carbonate (2×50 mL) and brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting oil is purified by flash chromatography over silica gel to provide 6-tert-butyl-nicotinic acid (1.1 g) as a white solid.

Workup

stirringthe resulting crystalline slurry stirred under nitrogen
temperatureThe reaction is cooled to 0° C.
extractionextracted with EtOAc (4×50 mL)
washThe pooled organic layers are washed with saturated sodium carbonate (2×50 mL) and brine
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated in vacuo
customThe resulting oil is purified by flash chromatography over silica gel

Sources & evidence

ORD record: ord-c52692c991994a418d2445ac8fdad6bd
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07947835B2

Reaction notes

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