Acetic Acid → Methyl 6-aminonicotinate

Participants

Reaction Steps

To a solution of 6-aminonicotinic acid (2.00 g, 14.48 mmol) dissolved in chloroform/MeOH (90 mL: 30 mL) was added (trimethylsilyl)diazomethane (2.0M in hexanes, 25 mL). After 15 minutes acetic acid (0.1 mL) was added and the solution was concentrated in vacuo to a residue. Trituration with EtOAc/Hex (2:1) provided methyl-6-aminonicotinate as a pale yellow solid after filtration. This material was used directly in the next step. To a solution of methyl-6-aminonicotinate (1.86 g, 12.22 mmol) dissolved in methylene chloride (90 mL) was added di-t-butyl dicarbonate (2.69 g, 12.34 mmol), 4-dimethylaminopyridine (0.15 g, 1.22 mmol) and triethylamine (2.00 mL, 14.66 mmol). After 14 h the reaction was diluted with EtOAc (400 mL) and washed with citric acid (1×50 mL, 10%), water (1×50 mL) and brine (1×50 mL) and was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (40×150 mm column of SiO2, EtOAc/Hex gradient elution 1:6, 1:5, 1:3) to to give the title compound as a white solid:

Provenance & Evidence