反应详情

温度

10 °C

To a solution of tert-butyl N-[2-(methoxy(methyl)amino)-2-oxo-ethyl]carbamate (2,455.3 g, 11.25 mol) in THF (9.0 L) is added 2.0M isopropylmagnesium chloride in THF (5.34 L, 10.69 mol) at −30° C. via an addition funnel over a period of 60 min such that the internal temperature does not exceed 0° C. The mixture is then warmed slowly to 10° C. and 0.5M cyclopropylmagnesium bromide in THF (27.0 L, 13.50 mol) is added via an addition funnel over a period of 1 h. The mixture is stirred at room temp 24 h. The mixture is cooled to 0° C. and quenched with 1.0M HCl to pH 5-6, then warmed to room temp and extracted with EtOAc (12 L and 10 L). The combined organic phase is washed successively with water (10 L) and brine (8 L), dried over Na2SO4, and filtered. The filtrate is evaporated under reduced pressure to afford 2.24 kg (100% yield) of the title compound as a light yellow oil which is used directly for the next step.

1. customdoes not exceed 0° C
2. temperatureThe mixture is cooled to 0° C.
3. customquenched with 1.0M HCl to pH 5-6
4. temperaturewarmed to room temp
5. extractionextracted with EtOAc (12 L and 10 L)
6. washThe combined organic phase is washed successively with water (10 L) and brine (8 L)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. customThe filtrate is evaporated under reduced pressure