反应详情

A microwave vial was charged with cis-4-(tert-butoxycarbonylamino)cyclohexanecarboxylic acid (0.24 g, 0.98 mmol), DMAP (0.12 g, 0.98 mmol) and Intermediate 33A (0.20 g, 0.98 mmol). The reactants were dissolved in DMF (1 mL) and DIC (0.15 mL, 0.98 mmol) was added. The reaction mixture was stirred at rt for 14 h. The reaction mixture was diluted in 3 mL of pyridine. The vial was capped and the reaction mixture was heated in the microwave at 145° C. for 20 minutes, allowed to cool to rt, diluted with EtOAc and washed with water and brine. The solution were concentrated under reduced pressure and purified by flash chromatography with EtOAc/hexanes to give Intermediate 33B (233 mg, 0.565 mmol, 57.9% yield) as a white solid. LCMS=434.1 [M+1], RT=2.43 min (Method B); 1H NMR (500 MHz, chloroform-d) δ ppm 8.19 (1H, d, J=1.93 Hz), 7.92 (1H, dd, J=8.53, 1.93 Hz), 7.56 (1H, d, J=8.25 Hz), 4.59 (1H, br. s.), 3.71 (1H, d, J=9.63 Hz), 3.14-3.22 (1H, m), 2.07-2.17 (2H, m), 1.92-2.02 (2H, m), 1.84 (2H, td, J=8.67, 4.13 Hz), 1.62-1.73 (2H, m), 1.44 (9H, s).

1. customThe vial was capped
2. temperaturethe reaction mixture was heated in the microwave at 145° C. for 20 minutes
3. temperatureto cool to rt
4. washwashed with water and brine
5. concentrationThe solution were concentrated under reduced pressure
6. custompurified by flash chromatography with EtOAc/hexanes