反应详情

温度

-60 °C

4(S)-(3,4-difluorophenyl)-5(S)-methyloxazolidin-2-one (2 g, 9.4 mmole) was dissolved in THF (20 ml) and cooled to −60° C. for the dropwise addition of n-BuLi (4 ml, 2.5 M in hexane). In a separate flask, p-nitrophenyl chloroformate was dissolved in 20 ml THF and cooled to −60° C. When the addition of n-BuLi was complete, the mixture was aged at −60° C. for 30 minutes. and then transferred via cannula to the p-nitrophenyl chloroformate solution. The reaction mixture was then allowed to warm to room temperature, and reaction progress was monitored by HPLC. After 2.5 hours, 3-(4-(4-fluorophenyl)piperidin-1-yl)propylamine (Example 1) (2.2 g, 9.4 mmole) in THF was added. After 3.5 hours at room temperature age, the solution was diluted with 100 ml water and extracted with 2×50 ml MTBE. The MTBE extractions were combined and washed with 2×50 ml 1M sulfuric acid. The aqueous washes were combined, rendered basic (pH=9-10) with 2 M sodium carbonate, and extracted with 2×100 ml MTBE. The MTBE layers were combined and concentrated, and the title compound was isolated by column chromatography on silica gel using 9:1 EtOAc:MeOH.

1. temperatureto warm to room temperature
2. customreaction progress
3. waitAfter 2.5 hours
4. waitAfter 3.5 hours at room temperature age
5. extractionextracted with 2×50 ml MTBE
6. extractionThe MTBE extractions
7. washwashed with 2×50 ml 1M sulfuric acid
8. extractionextracted with 2×100 ml MTBE
9. concentrationconcentrated