Methyl iodide → Tert-butyl(6-bromo-3-methoxypyridin-2-yl)(methyl)carbamate

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Reaction Steps

NaH (60% in oil, 1.90 g, 47.5 mmol) was added to cooled (5° C.) anhydrous 2-MeTHF (120 mL) under argon, followed by a solution of tert-butyl(6-bromo-3-methoxypyridin-2-yl)carbamate (4.80 g, 15.8 mmol) in anhydrous 2-MeTHF (40 mL) slowly, maintaining the reaction temperature below 15° C. Once the addition was complete the reaction was stirred for 15 min prior to addition of iodomethane (2.76 mL, 44.3 mmol). After stirring at rt for 21 h, further iodomethane (2.76 mL, 44.3 mmol) was added and the reaction mixture stirred at rt for 1 d. After cooling to 5° C. saturated aqueous NH4Cl and H2O (1:1, 160 mL) was added with caution. The mixture was stirred at rt for 15 min, the phases were separated and the aqueous phase extracted with EtOAc (2×200 mL). The combined organic phases were washed with brine, dried (Na2SO4) and concentrated in vacuo before purification by gradient flash chromatography, eluting with 5-25% EtOAc in heptane yielded tert-butyl(6-bromo-3-methoxypyridin-2-yl)(methyl)carbamate (4.52 g, 14.3 mmol) as a colourless oil.

Provenance & Evidence