反应详情

温度

70 °C

Dissolve (2S)-4-benzyl-2-(4-fluorophenyl)morpholine (948 g, 3.5 mol) in 1,2-dichloroethane (17 L). Heat the mixture to 70° C. and add 1-chloroethyl chloroformate (1500 g, 10.5 mol) drop-wise while heating. Stir the mixture at 70° C. for 3 h and then concentrate the mixture to give a residue. Dissolve the residue in MeOH (10 L) and heat to 70° C. while stirring for 1 h. Concentrate the solution under reduced pressure to give a residue. Slurry the residue with EtOAc (5 L); filter; and wash the solid with EtOAc (1 L) to provide an off white solid. Slurry the solid with 10:1 EtOAc/MeOH (10:1. 3 L); filter; collect the solid to provide the title compound as a white solid (300 g). Concentrate the mother liquor to provide additional material. Slurry the this material with a mixture of EtOAc/MeOH (2:1; 1 L) and filter to give an additional 105 g of the title compound as a white solid. Mix the product batches to give the title compound (405 g, 53%). MS (m/z): 182 (M-Cl). ee value 100% (AD-H 250 mm×4.6 mm×5 um column using 90:10 hexanes (with 0.02% DEA):ethyl alcohol at 25° C. with a flow rate of 1.0 mL/min).

1. temperaturewhile heating
2. concentrationconcentrate the mixture
3. customto give a residue
4. temperatureheat to 70° C.
5. stirringwhile stirring for 1 h
6. concentrationConcentrate the solution under reduced pressure
7. customto give a residue
8. filtrationfilter
9. washand wash the solid with EtOAc (1 L)
10. customto provide an off white solid
11. filtrationfilter
12. customcollect the solid