反应详情

温度

80 °C

To a stirred mixture of Zn powder (8.06 g, 6 eq) in dry THF at rt under N2 was slowly added TiCl4 (6.8 mL, 3 eq). The resulting mixture was heated to 80° C. and refluxed for 1 h. After cooling to rt, a mixture of propiophenone (8.2 g, 3.0 eq) and (6-chloropyridin-3-yl)(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)methanone (6.5 g, 1.0 eq) in dry THF was added. The resulting mixture was refluxed for additional 2 h, then quenched with saturated aq. Na2CO3 solution, extracted with EtOAc. The extract was dried, concentrated, and purified by column chromatography to give a Z/E mixture of the product (6.3 g, 92%, Z/E=1/1). The Z/E mixture was recrystallized in petroleum ether/CH2Cl2 to give the pure Z-isomer (2.8 g, 41% yield). 1H NMR (400 MHz, CDCl3) δ 7.85 (s, 1H), 7.06-7.25 (m, 8H), 6.97 (d, J=8.4 Hz, 1H), 6.83 (d, J=8.0 Hz, 2H), 2.51 (q, J=7.6 Hz, 2H), 0.94 (t, J=7.6 Hz, 3H); m/z=336 [M+1]+.

1. temperaturerefluxed for 1 h
2. temperatureAfter cooling to rt
3. additionwas added
4. temperatureThe resulting mixture was refluxed for additional 2 h
5. customquenched with saturated aq. Na2CO3 solution
6. extractionextracted with EtOAc
7. customThe extract was dried
8. concentrationconcentrated
9. custompurified by column chromatography
10. customto give
11. additiona Z/E mixture of the product (6.3 g, 92%, Z/E=1/1)
12. customThe Z/E mixture was recrystallized in petroleum ether/CH2Cl2
13. customto give the pure Z-isomer (2.8 g, 41% yield)