1,8-Diazabicyclo(5.4.0)undec-7-ene → (1R,2S,7R,8S)-5-(7-azidomethyl-1,1-dioxo-1,4-dihydro-1lambda6 thieno[2,3-e][1,2,4]thiadiazin-3-yl)-3-(4-fluoro-benzyl)-6-hydroxy-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one

Participants

Reaction Conditions

Reaction Steps

To a solution of (1R,2S,7R,8S)-3-(4-fluoro-benzyl)-6-hydroxy-5-(7-hydroxymethyl-1,1-dioxo-1,4-dihydro-1λ6-thieno[2,3-e][1,2,4]thiadiazin-3-yl)-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one (0.38 g, 0.76 mmol) in dichloromethane (9 mL) at 0° C. was added 1,8-diazabicyclo[5.4.0]undec-7-ene (0.60 mL, 4.03 mmol) and diphenylphosphoryl azide (0.84 mL, 3.88 mmol). The reaction was stirred at 25° C. overnight. The reaction was quenched with 1.0 M aqueous hydrochloric acid solution (10 mL). The resulting mixture was extracted with dichloromethane (3×10 mL). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified via flash column chromatography (Teledyne Isco RediSep column; 0-1% methanol in dichloromethane) to afford the desired product, (1R,2S,7R,8S)-5-(7-azidomethyl-1,1-dioxo-1,4-dihydro-1λ6-thieno[2,3-e][1,2,4]thiadiazin-3-yl)-3-(4-fluoro-benzyl)-6-hydroxy-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one (0.21 g, 0.40 mmol, 52%), as a white solid. 1H NMR (400 MHz, CDCl3) δ: 1.18-1.78 (6H, m), 2.56-2.57 (1H, m), 2.82-2.87 (2H, m), 3.47 (1H, d, J=9.6 Hz), 4.21 (1H, d, J=14.8 Hz), 4.67 (2H, s), 5.15 (1H, d, J=14.4 Hz), 7.00-7.07 (2H, m), 7.19-7.23 (2H, m), 7.32-7.36 (1H, m).

Provenance & Evidence