反应详情

温度

-10 °C

Benzyl {(1S)-2-[methoxy(methyl)amino]-1-methyl-2-oxoethyl}carbamate (6 kg, 22.5 mol) and 3,5-bis(trifluoromethyl)bromobenzene (4.85 L, 28.1 mol) are dissolved in anhydrous THF (24 L). The solution is purged with nitrogen to remove distilled oxygen. The solution is cooled to −10° C. and i-PrMgCl in THF (56.4 mol) is slowly added (2 h) to the reaction via addition funnel, maintaining a reaction temperature ≦−5° C. The solution is allowed to warm to 20° C. and aged overnight at 20° C. The reaction is then cooled to −10° C. under nitrogen and is quenched slowly over 2 h into 5N HCl (14 L) that is maintained at 0-5° C. MTBE (60 L) is added and the biphasic mixture is agitated for 5 min. After warming to 20-25° C., it is allowed to settle for 30 min, and then the layers are separated. The organic layer is washed with water twice (12 L).

1. customThe solution is purged with nitrogen
2. customto remove
3. distillationdistilled oxygen
4. customto the reaction
5. additionvia addition funnel
6. temperaturemaintaining a reaction temperature ≦−5° C
7. temperatureto warm to 20° C. and aged overnight at 20° C
8. temperatureThe reaction is then cooled to −10° C. under nitrogen
9. customis quenched slowly over 2 h into 5N HCl (14 L) that
10. temperatureis maintained at 0-5° C
11. additionMTBE (60 L) is added
12. temperatureAfter warming to 20-25° C.
13. waitto settle for 30 min
14. customthe layers are separated
15. washThe organic layer is washed with water twice (12 L)