Dichloromethane → HCID 86728136, compound

Participants

Reaction Steps

A 3-necked round bottom flask equipped with a mechanical stirrer, Claisen adapter with thermocouple and a nitrogen inlet was charged with 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 (4.00 g, 7.02 mmol, 2.85:1 ratio of diastereomers), sodium bicarbonate (1.180 g, 14.04 mmol), DCM (30 mL) and MeOH (10.00 mL), and the resulting solution was cooled to Tinternal<−65+/−1° C. Ozone was bubbled through the reaction mixture until starting material was consumed according to LCMS (˜1.5 h). The solution was purged with oxygen and then nitrogen, and sodium borohydride (0.531 g, 14.04 mmol) added in one portion. The cooling bath was removed, and the reaction mixture was allowed to warm to RT overnight. 2 mL acetone was added, followed by 10 mL sat. aq.NH4Cl. After stirring for 10 min, 5 mL water was added and the layers were separated. The organic portion was dried over magnesium sulfate, filtered and concentrated in vacuo to provide tert-butyl N-tert-butoxycarbonyl-N-[(3R)-3-(2-fluoro-5-nitro-phenyl)-2-(2-hydroxyethyl)-3,6,6-trimethyl-1,1-dioxo-2H-1,4-thiazin-5-yl]carbamate (4.04 g, 2.85:1 ratio of diastereomers) as a white solid that was used without further purification. LC/MS (ESI+) m/z=596.2 (M+Na).

Provenance & Evidence