反应详情

温度

160 °C

Cesium carbonate (2.308 g, 7.08 mmol) was added in one portion to (2-fluoro-5-iodophenyl)(4-methoxypiperidin-1-yl)methanone (41) (1.06 g, 2.92 mmol), diethyl malonate (1.329 mL, 8.76 mmol), 2-phenylphenol (0.099 g, 0.58 mmol) and copper(I) iodide (0.056 g, 0.29 mmol) in THF (10 mL) at 25° C. under nitrogen. The resulting mixture was stirred at 160° C. in the microwave reactor for 90 minutes. The reaction mixture was evaporated to dryness and redissolved in Et2O (200 mL), and washed sequentially with water (100 mL) and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% ethyl acetate in isohexane. Pure fractions were evaporated to dryness to afford the desired material as a colourless gum (2.03 g, 72% yield); 1H NMR (400.132 MHz, CDCl3) δ 1.25 (3H, t), 1.53-1.61 (1H, m), 1.67-1.74 (1H, m), 1.77-1.84 (1H, m), 1.89-1.97 (1H, m), 3.12-3.20 (1H, m), 3.36 (3H, s), 3.44-3.62 (3H, m), 3.59 (2H, s), 3.96-4.05 (1H, m), 4.15 (2H, q), 7.02-7.06 (1H, m), 7.26-7.33 (2H, m); m/z (LC-MS, ESI+), RT=1.08 (M+H 324.3).

1. customThe reaction mixture was evaporated to dryness
2. dissolutionredissolved in Et2O (200 mL)
3. washwashed sequentially with water (100 mL) and saturated brine (50 mL)
4. dry with materialThe organic layer was dried over MgSO4
5. filtrationfiltered
6. customevaporated
7. customto afford crude product
8. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 50% ethyl acetate in isohexane
9. customPure fractions were evaporated to dryness