Isobutylene oxide → HCID 131735337, compound

Participants

Reaction Conditions

Reaction Steps

To a 25-mL RBF was added tert-butyl N-tert-butoxycarbonyl-N-[(3R)-3-(2-fluoro-5-nitro-phenyl)-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-yl]carbamate (450 mg, 0.850 mmol) in THF (5.6 ml). The reaction solution was cooled to −78° C., then LHMDS (1.0M in THF; 2124 μl, 2.124 mmol) was added slowly. The brown solution was stirred for 15 min, then 1,1-dimethyloxirane (377 μl, 4.25 mmol) was added at −78° C. The reaction mixture was stirred from −78° C. to RT by removing dry-ice bath. 35 min later, it was quenched by 8 mL sat. aq. NH4Cl. The reaction mixture was diluted with water and extracted with EtOAc. The organic extract was washed with satd NaCl and dried over MgSO4. The solution was filtered and concentrated to give the crude material as a brown oil. The crude mixture was dissolved in 6 ml tBuOH and potassium tert-butoxide, 1.0M solution in THF (2.5 ml, 2.55 mmol). It was stirred at RT. 20 min later, 8 mL of aq. NH4Cl was added and extracted with EtOAc. The organic extract was concentrated and was purified using 40 g Puriflash column in 20% to 35% to 50% EtOAc/Heptanes to give 56 mg of tert-butyl ((4aR,11bR)-3,3,6,6,11b-pentamethyl-10-nitro-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (13% yield, less polar by TLC), and 90 mg of tert-butyl ((4aS,11bR)-3,3,6,6,11b-pentamethyl-10-nitro-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (22% yield, containing impurity, more polar by TLC). MS m/z=504.0 (M+Na).

Provenance & Evidence