Reaction Steps
To a suspension of 1B (82 mg, 0.228 mmol) in 5 mL of acetonitrile at rt was added DCC (47 mg, 0.228 mmol) followed byp-nitrophenol (63 mg, 0.456 mmol). The suspension was refluxed for 1 h, cooled to rt and filtered. The filtrate was concentrated under reduced pressure and the residue dissolved in EtOAc, washed with water and brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, EtOAc/Hexanes, 50:50 and 75:25) to afford the title compound (61 mg) as an off-white solid. 1H NMR (CD3OD) δ 2.21-2.23 (m, 2H), 2.37, 2.39 (s, 3H), 3.61-3.64 (m, 1H), 3.97-4.04 (m, 1H), 4.66, 4.68 (s, 1H), 4.79 (d, J=3.9, 1H), 7.45, 7.55 (d, J=8.3, 1H), 7.83 (d, J=8.3, 1H); 13C NMR (DMSO-d5) δ 15.47, 15.94, 35.32, 35.44, 48.21, 48.36, 69.77, 69.82, 73.74, 114.68, 115.59, 129.50, 132.70, 132.90, 134.25, 136.92, 138.96, 163.11, 163.59; HPLC a) column: Phenominex C18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA; 1 min hold, 4 mL/min UV detection at 220 nm, 2.65 min retention time; HPLC b) column: Shimadzu Shim-Pack VP-ODS C18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA, 1 min hold; 4 mL/min, UV detection at 220 nm, 2.52 min retention time (100%); HPLC c) column: Daicel Chiralcel OD 4.6×250 mm, Isocratic 25% Isopropanol/Hexanes, 30 min, 1 mL/min, UV detection at 220 nm, 11.86 min retention time (99%); MS (ES) m/z 340 [M−H]−.
