反应详情

温度

50 °C

To the solution of chloromethyl di-tert-butyl phosphate in Acetone (22.1 g from a 10% solution, 85.58 mmole), 15.5 g (103.24 mmole) of sodium iodide and 33.0 g (57.00 mmole) of netupitant were added and the solution heated at 50° C. for at 6-16 h. The precipitated salts were filtered off, the acetone distilled under reduced pressure and the crude product dissolved in 43.0 g of methanol and 43.0 g 1,4-dioxane. 12.6 g of HCl 4M in dioxane (113.85 mmole) were added, and then methanol is distilled off at 40° C. under reduced pressure. The solution is cooled at 5° C. and stirred at 5° C. for at least 2 h at 5° C. The product was isolated by filtration, purified by additional slurry in acetone (238 g), and filtered and washed with acetone (47 g) and pentane (2×72 g).

1. filtrationThe precipitated salts were filtered off
2. distillationthe acetone distilled under reduced pressure
3. dissolutionthe crude product dissolved in 43.0 g of methanol
4. distillationmethanol is distilled off at 40° C. under reduced pressure
5. temperatureThe solution is cooled at 5° C.
6. customThe product was isolated by filtration
7. custompurified by additional slurry in acetone (238 g)
8. filtrationfiltered
9. washwashed with acetone (47 g) and pentane (2×72 g)