832715-99-8

59-67-6

815-17-8

832715-99-8

Step 1: Preparation of 6-tert-butylnicotinic acid 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 stirred under nitrogen protection until a clear solution was formed. Subsequently, neopentanoic acid (1.83 g, 17.9 mmol) was added and stirring was continued for 10 minutes at room temperature under nitrogen protection. Silver nitrate (125 mg, 0.74 mmol) and ammonium persulfate (295 mg, 1.3 mmol) were added sequentially, the flask was wrapped in aluminum foil to protect from light, and the reaction mixture was heated to 90 °C under nitrogen protection. After 2 hours of reaction, the reaction was cooled to room temperature and the aqueous phase mixture was concentrated under reduced pressure to give a colorless solid. The solid was ground with tetrahydrofuran and filtered, the solid residue was recrystallized with methanol and filtered again. The two filtrates were combined and concentrated under reduced pressure. The crude product was purified by reversed-phase chromatography using an 85 g C-18 column eluting with a gradient of 10% aqueous acetonitrile to 100% acetonitrile. The product-containing fraction was collected and concentrated under reduced pressure. The residue was lyophilized in water to give 6-tert-butylnicotinic acid as a colorless solid (139 mg, 4% yield). LC/MS: m/z calculated value C10H13NO2 ([M+H]+): 180.2. measured value: 180.1 (positive ion mode, electrospray ionization).