Ammonium Chloride → HCID 131735328, compound

Participants

Reaction Conditions

Reaction Steps

To a 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 (200 mg, 0.378 mmol) and dry THF (2.5 ml). The reaction mixture was cooled to −78° C. and LHMDS (1 M in THF; 0.94 ml, 0.944 mmol) was added. The mixture was stirred fort 0 min and then (r)-(+)-1,2-epoxypropane (53 μl, 0.755 mmol) was added. The reaction mixture was stirred for 1 hr at −78° C. and then dry ice/acetone bath was removed. The mixture was allowed to warm up to RT and stirred for 1 h. It was quenched by 3 ml of 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 2 ml tBuOH and potassium tert-butoxide, 1.0 M solution THF (1.1 ml, 1.1 mmol). It was stirred at RT. 20 min later, 5 mL of sat. aq. NH4Cl was added and it was extracted with EtOAc. It was concentrated and was purified by silica gel chromatography eluting with 20% to 35% to 50% EtOAc in heptane to give tert-butyl ((4aR,6R,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 (50 mg, 0.107 mmol, 28.3% yield) and tert-butyl ((4aS,6R,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 (27 mg, 0.058 mmol, 15.29% yield). MS m/z=490.0 (M+23).

Provenance & Evidence