反应详情

温度

-78 °C

To a stirred, cooled (−78° C.) solution of (2,4-difluoro-phenyl)-carbamic acid tert-butyl ester (5 g) in THF (50 ml) under an argon atmosphere was added dropwise a 1.6 M solution of BuLi in hexanes (28.6 ml) for 20 min (temperature below −68° C. during the addition). When addition was complete, the mixture (turning to orange, then to light red) was stirred at −78° C. for 1 h 30. DMF (7.55 ml) was then added for 10 min (temperature below −70° C.) and stirring at −78° C. was continued for 15 min. As the mixture had turned to a compact mas (no more stirring), it was allowed to warm to room temperature. Water (50 ml) was added and the pH was set to 3 by the dropwise addition of 3 N HCl. EtOAc (50 ml) was added. The organic phase was washed with water and brine dried over MgSO4, filtered and concentrated. The crude product was purified by flash chromatography (cyclohexane=>cyclohexane/EtOAc 85:15) to give (2,4-difluoro-3-formyl-phenyl)-carbamic acid tert-butyl ester (1.75 g) as an off-white solid.

1. additionduring the addition)
2. additionWhen addition
3. stirringstirring at −78° C.
4. waitwas continued for 15 min
5. stirringno more stirring), it
6. temperatureto warm to room temperature
7. washThe organic phase was washed with water and brine
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude product was purified by flash chromatography (cyclohexane=>cyclohexane/EtOAc 85:15)