Hydrochloric Acid → 5-Azaindole

Participants

Reaction Conditions

Reaction Steps

A solution of 4-tert-butoxycarbonylamino-3-methylpyridine (step (a), 1.0 g, 4.8 mmol) in tetrahydrofuran (40 ml) was cooled to -40° C. and tert-butyllithium (8.0 ml 1.7M in pentane, 13.6 mmol) added at such a rate as to keep the temperature below -30° C. The dark orange mixture was stirred at -40° C. for 1 hour and then treated with dimethylformamide (0.56 ml, 7.2 mmol). The mixture was warmed to 20° C. and stirred for 1 hour. 5.5M hydrochloric acid (15 ml) was added and the mixture heated at 45°-50° C. for 1 hour. The mixture was cooled to 0° C., isopropyl acetate (25 ml) added and the whole neutralised with 5M sodium hydroxide (15 ml). The phases were separated and the aqueous layer was extracted with isopropyl acetate (25 ml). The combined organic fractions were washed with saturated brine (25 ml), dried (Na2SO4), filtered and concentrated, in vacuo, to residue. The crude product was purified by chromatography on silica gel (95% methylene chloride/5% methanol) to afford the title compound as an off-white solid; yield: 0.45 g (79%). mp. 108°-110° C. [Lit. mp 109°-110° C.].

Provenance & Evidence