反应详情

To a solution of Example 25A (440 mg, 0.72 mmol) in dichloromethane (1 mL) was added trifluoroacetic acid (0.5 mL) and stirred at room temperature for 2 hours. The reaction was concentrated, taken up in dichloromethane and washed with saturated sodium bicarbonate solution. The aqueous layer was washed with dichloromethane. The combined organic layers were dried over sodium sulfate, and concentrated in vacuo. The residue was purified by preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 gm particle size) using a gradient of 10-100% acetonitrile (A) and 10 mM ammonium acetate in water (B), at a flow rate of 2.0 mL/min (0-0.1 min 10% A, 0.1-2.6 min 10-100% A, 2.6-2.9 min 100% A, 2.9-3.0 min 100-10% A. 0.5 min post-nm delay) to obtain the title compound (350 mg , 95%). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.33 (s, 9 H) 1.39-1.53 (m, 1 H) 1.57-1.69 (m, 1 H) 1.76-1.95 (m, 5 H) 2.40-2.46 (m, 1 H) 2.63-2.74 (m, 2 H) 2.80-2.89 (m, 2 H) 3.58-3.69 (m, 1 H) 3.75-3.82 (m, 1 H) 3.95-4.09 (m, 2 H) 4.18-4.31 (m, 3 H) 7.24-7.29 (m, 2 H) 7.74 (dd, J=8.92, 2.58 Hz, 1 H) 7.99 (d, J=2.38 Hz, 1 H); MS (DCI/NH3) m/z 512 (M+H)+.

1. concentrationThe reaction was concentrated
2. washwashed with saturated sodium bicarbonate solution
3. washThe aqueous layer was washed with dichloromethane
4. dry with materialThe combined organic layers were dried over sodium sulfate
5. concentrationconcentrated in vacuo
6. customThe residue was purified by preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 gm particle size)