反应详情

To a solution of 3,5-difluoropicolinic acid (16.40 g, 103.1 mmol), 3-fluoroazetidine (8.59 g, 114 mmol) and triethylamine (27.70 ml, 199.0 mmol) in 100 mL of DMF was added HATU (45.40 g, 119.0 mmol). The mixture was stirred at room temperature for 3 hr, quenched with water, extracted with 3× EtOAc. The combined organic layer was washed with 2×H2O, dried with Na2SO4, and concentrated to provide an oil that was purified by Biotage eluting with 25-40% EtOAc in hexanes to give a yellow solid (11.49 g, 46.3% yield). 1H NMR (400 MHz, CDCl3) δ 8.34 (d, J=2.53 Hz, 1 H) 7.31-7.46 (m, 1 H) 5.27-5.52 (m, 1 H) 4.62-4.79 (m, 1 H) 4.42-4.59 (m, 2 H) 4.22-4.38 (m, 1 H); MS for C9H7F3N2O m/z 217.00 (M+H)+

1. customquenched with water
2. extractionextracted with 3× EtOAc
3. washThe combined organic layer was washed with 2×H2O
4. dry with materialdried with Na2SO4
5. concentrationconcentrated
6. customto provide an oil that
7. customwas purified by Biotage
8. washeluting with 25-40% EtOAc in hexanes