Ethylene Oxide → HCID 131735334, compound

Participants

Reaction Conditions

Reaction Steps

To an oven dried flask was added tert-butyl N-[(4aR,11bR)-4a-fluoro-3,3,11b-trimethyl-10-nitro-4,4-dioxo-5,6-dihydro-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (See procedure for Intermediate 24, Step 1) (0.260 g, 0.475 mmol) and THF (3.17 mL). The resulting mixture was cooled to −78° C. and LHMDS (1 M in THF; 0.712 mL, 0.712 mmol) was added and the mixture was stirred for 40 minutes and then oxirane (7.91 mL, 9.50 mmol) was added. The dry ice/acetone bath was removed and the mixture was stirred for 30 minutes. The resulting mixture was treated with saturated aqueous ammonium chloride and extracted with EtOAc. The organic layer was concentrated and the crude material was eluted through a silica gel column using 10-50% EtOAc/Heptane. The desired fractions were combined and concentrated down to yield tert-butyl ((4aR,11bR)-4a-fluoro-3,3,11b-trimethyl-10-nitro-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (0.090 g, 0.191 mmol, 40.2% yield)). ESI MS: 494.1 [M+Na] and a mixture of tert-butyl ((4aR,11bR)-4a-fluoro-3,3,11b-trimethyl-10-nitro-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate and tert-butyl N-[(4aR,11bR)-4a-fluoro-3,3,11b-trimethyl-10-nitro-4,4-dioxo-5,6-dihydro-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (89 mg, 0.156 mmol, 32.8% yield) ESI MS: 494.1/594.1 [M+Na].

Provenance & Evidence