反应详情

温度

100 °C

A mixture of methyl 4-cyclobutyl-5-iodo-2-methylbenzoate (compound 6.3, 4.17 g, 12.6 mmol), Zn(CN)2 (2.96 g, 25.2 mmol) and Pd(PPh3)4 (0.73 g, 0.63 mmol) in DMF (30 mL) was degassed and the flask was charged with argon. The mixture was heated at 100° C. under argon overnight. After cooling to ambient temperature, the mixture was quenched with saturated aq. FeSO4 (20 mL) and diluted with EtOAc (200 mL). The greenish solid was removed by filtration through Celite® and the filtrate was partitioned between water and EtOAc. The organics was washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified using silica gel column chromatography (hexanes:EtOAc 30:1 to 20:1) to yield the title compound as a white solid (2.55 g, 88%). 1H NMR (400 MHz, CDCl3) δ 8.16 (s, 1H), 7.28 (s, 1H), 3.90 (s, 3H), 3.86-3.82 (m, 1H), 2.68 (s, 3H), 2.55-2.45 (m, 2H), 2.27-2.04 (m, 3H), 1.89-1.87 (m, 1H).

1. customwas degassed
2. additionthe flask was charged with argon
3. temperatureAfter cooling to ambient temperature
4. customthe mixture was quenched with saturated aq. FeSO4 (20 mL)
5. additiondiluted with EtOAc (200 mL)
6. customThe greenish solid was removed by filtration through Celite®
7. customthe filtrate was partitioned between water and EtOAc
8. washThe organics was washed with brine
9. dry with materialdried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe residue was purified