General procedure for the synthesis of methyl 4-chloro-6-methoxypyridine-2-carboxylate from methyl 4-amino-6-methoxy-pyridine-2-carboxylate: to a mixture of 1.25 mL (10.5 mmol) of tert-butyl nitrite and 1.42 g (10.5 mmol) of copper(II) chloride in 40 mL of acetonitrile was added slowly, dropwise, at 40 °C, 1.20 g (6.59 mmol) of 4- methyl amino-6-methoxy-pyridine-2-carboxylate dissolved in 10 mL of acetonitrile. The reaction mixture was stirred at 80 °C for 1 h and then poured into ice water, acidified with 4 M aqueous HCl and extracted with EtOAc. The combined organic phases were dried with anhydrous sodium sulfate, filtered and concentrated in vacuum. The crude product was purified by fast chromatography (eluent ratio: petroleum ether/EtOAc 3/1→2/1). A product of 650 mg was obtained in 49% yield. eSI-MS: m/z = 202 (M + H)+. hPLC retention time: 1.12 min (Method 5).
