反应详情

温度

110 °C

A mixture of (3,5-difluoropyridin-2-yl)(3-fluoroazetidin-1-yl)methanone (7.49 g, 34.60 mmol), methyl 4-hydroxy-2,2-dimethyl-2,3-dihydrobenzofuran-6-carboxylate (7.69 g, 34.60 mmol) and Cs2CO3 (16.90 g, 52.0 mmol) in DMF was heated to 110° C. for 30 min, cooled to room temperature, quenched with H2O and extracted with 3×EtOAc. The combined organic layer was washed with 2×H2O, dried over Na2SO4 and concentrated. The residue was purified by Biotage eluting with 25-40% EtOAc in hexanes to give a white foam with ˜20% impurity (10.49 g, 72% yield). 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J=2.27 Hz, 1 H) 7.21-7.30 (m, 2 H) 6.98-7.06 (m, 1 H) 5.26-5.49 (m, 1 H) 4.64-4.77 (m, 1 H) 4.46-4.60 (m, 1 H) 4.28-4.42 (m, 1 H) 4.07-4.23 (m, 1 H) 3.88 (s, 3 H) 2.91 (s, 2 H) 1.49 (s, 6 H); LCMS for C21H20F2N2O5 m/z 419.20 (M+H)+.

1. temperaturecooled to room temperature
2. customquenched with H2O
3. extractionextracted with 3×EtOAc
4. washThe combined organic layer was washed with 2×H2O
5. dry with materialdried over Na2SO4
6. concentrationconcentrated
7. customThe residue was purified by Biotage
8. washeluting with 25-40% EtOAc in hexanes
9. customto give a white foam with ˜20% impurity (10.49 g, 72% yield)