Methyl iodide → 5-Azaindole

Participants

Reaction Conditions

Reaction Steps

4-tert-Butoxycarbonylamino-3-methylpyridine A solution of 4-tert-butoxycarbonylaminopyridine (10.0 g, 51.5 mmol) in tetrahydrofuran (150 ml) was cooled to -30° C. and n-butyllithium (45.3 ml, 2.5M in hexane, 113.3 mmol) was added at such a rate as to keep the temperature below -20° C. The mixture was stirred at 0° C. for 3 hours, the slurry cooled to -70° C. and a solution of methyl iodide (8.77 g, 61.8 mmol) in tetrahydrofuran (25 ml) added. The mixture was warmed to 20° C. and stirred for 1 hour. The mixture was quenched with water (100 ml) and extracted with ethyl acetate (2×100 ml). The combined ethyl acetate fractions were washed with saturated brine (100 ml), dried (Na2SO4), filtered and concentrated in vacuo. The crude product was chromatographed on silica gel (95% methylene chloride/5% methanol) and then swished in hot hexane to afford the title compound as a pale yellow solid; yield: 5.75 g (54%). mp 124°-126° C.; Analysis Found: C, 63.35; H, 7.72; N, 13.44. C11H16N2O2 : requires C, 63.44; H, 7.74; N, 13.45%; 1H NMR (CD2Cl1 /TMS) δ1.52 (9H, s), 2.22 (3H, s), 6.92 (1H, br.s), 7.97 (1H, d, J=5.6 Hz), 8.28 (1H, s), 8.33 (1H, d, J=5.6 Hz).

Provenance & Evidence