Reaction Steps
Boc methylenedioxybenzenesulfonamide bis-methoxyethylamine tethered product (18) (0.023 g, 0.033 mmol) was dissolved in DCM (1 mL). Trifluoroacetic acid (0.5 mL) was added dropwise, and the reaction was stirred at room temperature for 1 hour. The solvent was removed in vacuo, and the resultant orange oil was dissolved in DCM (1 mL) and the solution cooled to 0° C. using an ice bath. Diisopropylethylamine (0.173 mL, 0.99 mmol) was added dropwise with stirring, followed by (3R,3aS,6aR) hexahydrofuro[2,3-b]furan-2-yl 4-nitrophenyl carbonate (0.012 g, 0.040 mmol) in one portion as a solid. After 5 minutes, the ice bath was removed and the reaction mixture was allowed to warm to room temperature with stirring overnight. The solvent was removed in vacuo, and the resultant yellow oil was purified by flash column:chromatography (4:1 ethyl acetate/hexane to ethyl acetate to 9:1 DCM/methanol) to give bis-THE methylenedioxybenzenesulfonamide bis-methoxyethylamine tethered product (51) (0.022 g, 89%) as a yellow foam: Rf=0.50 (9:1 DCM/methanol); 1H NMR (CDCl3): 7.33 (1H, dd, J=8.2, 1.8 Hz), 7.17 (1H, d, J=1.8 Hz), 7.13 (2H, d, J=8.6 Hz) 6.89 (1H, d, J=8.2 Hz), 6.80 (2H, d, J=8.6 Hz), 6.09 (2H, s), 5.65 (1H, 8, J=5.2 Hz), 5.08-4.98 (2H, m), 4.35-4.24 (2H, m), 4.00-3.90 (1H, m), 3.90-3.63 (6H, m), 3.61-3.49 (2H, m), 3.42-3.31 (2H, m), 3.35 (6H, s), 3.16-3.07 (2H, m), 3.05-2.88 (4H, m), 2.88-2.74 (2H, m), 1.83 (1H; septet, J=6.6 Hz), 1.74-1.54 (1H, m), 1.48-1.35 (5H, m); 0.92 (3H, d, J=6.6 Hz), 0.88 (3H, d, J=6.6 Hz), OH signal not observed; coupled LCMS showed the product as a single major peak with m/z 752 [M+H]+; HPLC (205 nm) showed the material as a single major peak at RT of 1.92 min. (purity=91%).
