Sodium hydride → HCID 86728112, compound

Participants

Reaction Steps

To a solution of tert-butyl N-tert-butoxycarbonyl-N-[(3S)-3-(fluoromethyl)-3-(2-fluoro-5-nitro-phenyl)-2-(3-hydroxypropyl)-6,6-dimethyl-1,1-dioxo-2H-1,4-thiazin-5-yl]carbamate (1.95 g, 3.30 mmol) in THF:DMF (10:1, 44 mL) at 0° C. was added NaH (264 mg, 6.60 mmol, 60% suspension in mineral oil) portion wise. The reaction mixture was stirred at RT for 1 h and an additional amount of NaH was added (264 mg, 6.60 mmol, 60% suspension in mineral oil). The reaction mixture was stirred at RT for 1 h, quenched with satd. aqueous NH4Cl, and diluted with EtOAc. Water was added to dissolve solids, and the organic layer was separated. The organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude mixture was purified by silica gel chromatography using a 0-25% EtOAc/hexanes gradient to afford the less polar cis-isomer, tert-butyl N-[(4aS,11bS)-11b-(fluoromethyl)-3,3-dimethyl-10-nitro-4,4-dioxo-5,6-dihydro-4aH-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (647 mg, 34%) as a white solid, LC/MS (ESI+) m/z=594 (M+Na), and the more polar trans-isomer, tert-butyl N-[(4aS,11bS)-11b-(fluoromethyl)-3,3-dimethyl-10-nitro-4,4-dioxo-5,6-dihydro-4aH-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (594 mg, 31%) as a white solid. LC/MS (ESI+) m/z=594 (M+Na).

Provenance & Evidence