反应详情

温度

65 °C

To a solution of (R)-2-(4-cyano-phenyl)-1-(3,5-dichloro-4-fluoro-phenylcarbamoyl)-1-methyl-ethyl-ammonium toluene-4-sulfonate (87.7 g, 162.9 mmol) and (2,2-dimethoxy-ethyl)-carbamic acid phenyl ester (40.4 g, 179 mmol) in DMSO (162 mL) was added Na3PO4 (29.4 g, 179 mmol) and N-methylmorpholine (3.04 mL, 27.7 mmol). The solution was heated to 65° C. and stirred for 6 h. The solution was cooled to 20° C. and transferred to a separatory funnel with aqueous Na2CO3 (3 wt %, 500 mL) and EtOAc (500 mL), forming a triphasic system after shaking. The bottom two layers were removed. The top organic layer was washed with 3% aqueous NaCl (500 mL), dried with Na2SO4 and concentrated in vacuo keeping internal temperature lower than 40° C. A mixture of heptane and EtOAc (10:1 heptane:EtOAc, 20 mL) was added and the resulting slurry was stirred at 22° C. for 16 h. The slurry was filtered and the solids were washed with a 10:1 mixture of heptane/EtOAc (2×100 mL) to give 61.6 g of the title compound as a white solid, m/z 497.7 [M+H]+.

1. temperatureThe solution was cooled to 20° C.
2. customforming a triphasic system
3. stirringafter shaking
4. customThe bottom two layers were removed
5. washThe top organic layer was washed with 3% aqueous NaCl (500 mL)
6. dry with materialdried with Na2SO4
7. concentrationconcentrated in vacuo
8. customlower than 40° C
9. additionA mixture of heptane and EtOAc (10:1 heptane:EtOAc, 20 mL)
10. additionwas added
11. stirringthe resulting slurry was stirred at 22° C. for 16 h
12. filtrationThe slurry was filtered
13. washthe solids were washed with a 10:1 mixture of heptane/EtOAc (2×100 mL)