Cyclopropane → tert-butyl N-[(4aR,11bR)-10-[[5-(cyclopropylmethoxy)pyrazine-2-carbonyl]amino]-3,3,11b-trimethyl-4,4-dioxo-5,6-dihydro-4aH-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]carbamate

Participants

Reaction Steps

A solution of hydroxymethyl)cyclopropane (0.10 mL, 1.20 mmol) in THF (1.4 mL) was cooled to 0° C. and treated with sodium hydride (60% wt; 36.1 mg, 0.90 mmol). The reaction was stirred for 30 minutes and then a solution of tert-butyl N-[(4aR,11bR)-10-[(5-chloropyrazine-2-carbonyl)amino]-3,3,11b-trimethyl-4,4-dioxo-5,6-dihydro-4aH-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]carbamate (113 mg, 0.20 mmol) in 1 mL of THF was added. The reaction was stirred at ambient temperature for 1 hour. The reaction was treated with aqueous ammonium chloride and extracted with ethyl acetate. The organic portion was concentrated. The resulting crude was purified by column chromatography, eluting with 10-50% ethyl acetate/heptane to afford the title compound (100 mg, 0.17 mmol, 83%) as an off-white solid. MS m/z=600.2 (M+H).

Provenance & Evidence