Ammonium Chloride → HCID 131735332, compound

Participants

Reaction Conditions

Reaction Steps

To a 25-mL round-bottomed dry flask 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 (420 mg, 0.793 mmol) in THF (5 ml). The reaction solution was cooled to −78° C., then LHMDS (1 M in THF; 2.0 ml, 2.0 mmol) was added slowly. It was stirred for 20 min, then (S)-2-methyloxirane (92 μl, 1.586 mmol) was added at −78° C. The reaction mixture was stirred from −78° C. to 0° C. After 15 min, it was quenched by sat. aq. NH4Cl. The reaction mixture was diluted with water and extracted with EtOAc. The organic extract was washed with brine 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 4 ml tBuOH and potassium tert-butoxide, 1.0M solution in THF (2.4 ml, 2.4 mmol) was added. It was stirred at RT. 50 min later, 5 ml of sat. NH4Cl was added and the reaction mixture was extracted with EtOAc. It was concentrated and was purified by silica gel chromatography using 20% to 35% to 50% EtOAc/heptane to give 70 mg of tert-butyl ((4aR,6S,11bR)-3,3,6,11b-tetramethyl-10-nitro-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (less polar peak by TLC) and 50 mg of tert-butyl ((4aS,6S,11bR)-3,3,6,11b-tetramethyl-10-nitro-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (more polar peak by TLC). MS m/z=490.2 (M+23).

Provenance & Evidence