Allyl bromide → HCID 86728135, compound

Participants

Reaction Steps

A 3-necked RBF equipped with a mechanical stirrer, Claisen adapter with thermocouple and a nitrogen inlet was charged with 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 (8.8 g, 16.62 mmol) and THF (80 mL). The yellow solution was cooled to Tinternal−72+/−1° C. using a dry ice/IPA bath. KHMDS, 1M in THF (24.93 mL, 24.93 mmol) was added dropwise via cannula over ˜15 min keeping Tinternal<−72+/−1° C. The reaction mixture became dark brown, and was stirred at Tinternal˜−72+/−1° C. for 45 min. Allyl bromide (2.157 mL, 24.93 mmol) was added via syringe over 3 min, and stirring was continued at Tinternal<−75° C. for 75 min. 10 mL saturated aq. NH4Cl was added, the cooling bath was removed, and the reaction mixture was allowed to warm to RT. Water was added until all solids were dissolved, and the layers were separated. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude material was purified via silica gel chromatography (heptane/EtOAc: 100/0 to 40/60+5% DCM isocratic) to provide tert-butyl N-[(3R)-2-allyl-3-(2-fluoro-5-nitro-phenyl)-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-yl]-N-tert-butoxycarbonyl-carbamate (8.93 g, 2.85:1 ratio of diastereomers) as an off-white solid. LC/MS (ESI+) m/z=592.2 (M+Na).

Provenance & Evidence