Methyl iodide → tert-butyl 4-methylpyridin-3-ylcarbamate

Participants

Reaction Conditions

Reaction Steps

A solution of 3-tert-butoxycarbonylaminopyridine (13.5 g, 69.5 mmol) in tetrahydrofuran (300 ml) was cooled to -70° C. and treated with tert-butyllithinum (102.2 ml, 1.7M in pentane, 173.7 mmol) at such a rate as to maintain the temperature at below -60° C. The mixture was aged at -60° C. to -70° C. for 3.5 hours and then treated with a solution of methyl iodide (11.2 g, 79.1 mmol) in tetrahydrofuran (50 ml) while keeping the temperature below -60° C. The mixture was stirred at -50° C. to -60° C. for 30 minutes, warmed to -30° C. and quenched with water (300 ml). The mixture was extracted with ethyl acetate (2×300 ml) and the combined organic fractions were washed with saturated brine (200 ml), dried (Na2CO3), filtered and concentrated in vacuo to residue. The crude product was purified by chromatography on silica gel (50% ethyl acetate/50% hexane) and swished in hot hexane to afford the title compound as a pale beige crystalline solid; yield: 7.34 g (51%); mp. 91°-93° C.; Analysis Found: C, 63.44; H, 7.72; N, 13.38. C11H16N2 O2 requires C, 63.44; H, 7.74; N, 13.45%. 1H NMR (CD2 Cl2 /TMS) δ1.50 (9H, s), 2.26 (3H, s), 7.12 (2H, d+br.s, J=5.0 Hz), 8.22 (1H, d, J=5.0 Hz), 8.80 (1H, s).

Provenance & Evidence