Reaction Steps
TFA (5 mL) was added to a solution containing crude 116 (0.9 g) in DCM (20 mL) at 0° C. After 90 min, another portion of TFA (2 mL) was added. After 75 min, the reaction mixture was carefully quenched by the addition of saturated aqueous NaHCO3. The mixture was then diluted with EtOAc and water and the layers were separated. The organic phase was washed three times with aqueous NaHCO3 then once with brine. The combined aqueous washes were back-extracted with EtOAc and the combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by reverse-phase HPLC [2″ Dynamax C18; Method: 10-55% ACN/water containing 0.1% HOAc over 30 min; Flow: 40 mL/min]. The product-containing fractions were pooled, frozen, and lyophilized to afford 410 mg (53% from 115) of 117 as a white-colored solid. 1H NMR (300 MHz, d6-DMSO), mixture of carbamate rotomers: δ7.67 (d, J=8.7 Hz, 1H), 7.34-7.28 (m, 5H), 5.17-5.05 (m, 2H), 4.52 (m, 2H), 4.34 (m, 1H), 4.00 (m, 1H), 3.75 (m, 1H), 3.33 (m, 1H), 3.14-3.01 (m, 2H), 2.35 (br s, 3H), 2.30 (m, 1H), 1.90 (m, 1H), 1.69-1.60 (m, 5H), 1.27 (d, J=6.9 Hz, 3H), 1.18-0.94 (m, 5H) ppm. 13C NMR (75 MHz, d6-DMSO), mixture of carbamate rotomers: δ174.7, 174.4 172.9, 170.1, 170.0, 154.1, 154.0, 137.5, 129.1, 128.5, 128.2, 128.1, 66.7, 66.6, 63.0, 61.9, 61.6, 60.9, 59.5, 55.2, 54.7, 46.7, 46.1, 45.6, 41.5, 34.5, 32.3, 31.2, 30.7, 30.1, 29.6, 29.5, 28.9, 28.7, 26.4, 26.2, 26.1, 26.0, 22.0, 19.5, 19.4 ppm. Mass spectrum, m/z [471.0] (M+H)+.
