反应详情

温度

-5 °C

To a solution of dichloromethylphosphine (6.61 g, 57 mmol, 1.0 equiv.) in THF (50 mL) was added dropwise 1.0 M tBuMgCl (57 mL, 57 mmol, 1.0 equiv.) over 1 h while controlling the reaction temperature <−10° C. The mixture was stirred at −10 to 0° C. for 1 h and then warmed to 25° C. over 1 h and stirred at 25° C. for at least 1 h. To a solution of 1,3-dimethoxybenzene (9.37 g, 68 mmol, 1.2 equiv.) in THF (50 mL) in a separated flask was added 1.6 M BuLi (42.4 mL, 68 mmol, 1.2 equiv.) over 1 h while controlling the temperature <0° C. The mixture was further stirred at 0° C. for 0.5 h. To the aforementioned mixture of dichloromethylphosphine and tBuMgCl was added dropwise the mixture of in situ generated 2,6-dimethoxyphenyllithium made above over 0.5 h while controlling the reaction temperature <25° C. The resulting mixture was further stirred at 25° C. for 1 h. To the mixture was added dropwise 30% H2O2 over 10 min at 0° C. and the mixture was further stirred at 25° C. for 0.5 h, and then quenched with addition of 2 N HCl (300 mL) and dichloromethane (300 mL). The dichloromethane layer was washed with brine (300 mL), dried over magnesium sulfate, and purified by column chromatography (eluents: EtOAc to EtOAc/MeOH 4/1; monitored at 290 nm) to provide 1 as a thick oil (9.5 g, 37 mmol, 65%). 1: 1HNMR (400 MHz, CDCl3): δ=7.41 (m, 1H), 6.60 (dd, J=8.4, 3.8 Hz, 2H), 3.84 (s, 6H), 1.83 (d, J=13.2 Hz, 3H), 1.18 (d, J=15.4 Hz, 9H); 31PNMR (162 MHz, CDCl3): δ=51.4; 13CNMR (100 MHz, CDCl3): δ=163.1 (d, J=1.0 Hz), 133.7 (d, J=1.0 Hz), 107.3 (d, J=82 Hz), 104.5 (d, J=6 Hz), 55.65, 34.6 (d, J=72 Hz), 24.4 (d, J=1.6 Hz), 15.8 (d, J=69 Hz); ESI-MS: m/z 257 [M+H]+.

1. customthe reaction temperature <−10° C
2. temperaturewarmed to 25° C. over 1 h
3. stirringstirred at 25° C. for at least 1 h
4. customthe temperature <0° C
5. stirringThe mixture was further stirred at 0° C. for 0.5 h
6. additionwas added dropwise
7. additionthe mixture of in situ
8. custommade above over 0.5 h
9. customthe reaction temperature <25° C
10. stirringThe resulting mixture was further stirred at 25° C. for 1 h
11. stirringthe mixture was further stirred at 25° C. for 0.5 h
12. customquenched with addition of 2 N HCl (300 mL) and dichloromethane (300 mL)
13. washThe dichloromethane layer was washed with brine (300 mL)
14. dry with materialdried over magnesium sulfate
15. custompurified by column chromatography (eluents: EtOAc to EtOAc/MeOH 4/1; monitored at 290 nm)