反应详情

A mixture of Example 294A (0.085 g, 0.195 mmol), (benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (0.122 g, 0.234 mmol), triethylamine (0.109 mL, 0.780 mmol), and piperidin-4-ol.hydrochloride (0.032 g, 0.234 mmol) in N,N-dimethylformamide (2 mL) was stirred for 3 hours. The mixture was treated with water and brine and extracted with ethyl acetate (twice). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, concentrated, and purified on silica gel using the ISCO Companion eluting with dichloromethane/methanol/ammonium hydroxide (18:1:0.1 to 9:1:0.1) to give the title compound. 1H NMR (400 MHz, Methanol-d4) δ 1.33-1.60 (m, 2H), 1.79-1.94 (m, 2H), 2.56 (bs, 2H), 2.73-2.80 (m, 2H), 3.06-3.18 (m, 1H), 3.27-3.30 (m, 2H), 3.32-3.43 (m, 2H), 3.76 (s, 3H), 3.78-3.98 (m, 2H), 4.03-4.12 (m, 1H), 4.56 (d, J=1.1 Hz, 1H), 6.16 (s, 1H), 6.34-6.40 (m, 1H), 6.99-7.24 (m, 3H), 8.06 (d, J=2.9 Hz, 1H). MS (ESI+) m/z 483.1 (M+H)+.

1. extractionextracted with ethyl acetate (twice)
2. washThe combined organic layers were washed with brine
3. dry with materialdried over magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. custompurified on silica gel using the ISCO Companion
7. washeluting with dichloromethane/methanol/ammonium hydroxide (18:1:0.1 to 9:1:0.1)