Ammonia → Sumatriptan

Participants

Reaction Steps

To a stirred slurry of calcium turnings (243 mg, 6 mmol) in tetrahydrofuran (4 ml) at −40° C. was condensed liquid ammonia (4 ml). The blue bronze was stirred at −50 to −40° C. for a further 15 min, before a solution of 1-[1-benzyl-3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]-N-diphenylmethyl-N-methylmethanesulfonamide (from step (e), 836 mg, 1.5 mmol) in tetrahydrofuran (2 ml) was added dropwise, maintaining the temperature below −40° C. The dark blue solution was stirred at −40° C. for a further 30 minutes, before saturated ammonium chloride solution (10 ml) was added dropwise and the grey solution warmed to ambient temperature. Water (10 ml) was then added and the white slurry stirred for 15 min, before being filtered in vacuo. The solid was then dissolved in 5N HCl (12 ml) and the resulting orange solution extracted with ethyl acetate (10 ml). The pH of the aqueous phase was then adjusted (pH=10) with 10N NaOH which resulted in precipitation. The solid was filtered and dried in vacuo at 50° C. overnight to yield the title compound (250 mg, 56%) as a white solid. m.p. 159-163° C.

Provenance & Evidence