反应详情

DCM (33 L) and N-methylpiperazine (21.45 L, 193.4 mol) were stirred at 25° C. and the solution from step 8 added over a minimum of 30 mins such that temperature 20-30° C. After stirring the solution for a further 30 mins water (55 L) was added and the organic phase was washed with water (2×55 L). The product was extracted into 0.8M HCl (66 L) and the layers separated. The aqueous phase was washed with DCM (55 L) and then basified with 2M NaOH to pH 10-11 and the product was extracted into EtOAc (2×55 L). The combined organic phase were filtered to remove solids and the evaporated followed by azeotroping with toluene and drying to constant weight to give the title compound, 6.63 kg (47% yield, 98% pure by hplc).

1. additionwas added
2. washthe organic phase was washed with water (2×55 L)
3. extractionThe product was extracted into 0.8M HCl (66 L)
4. customthe layers separated
5. washThe aqueous phase was washed with DCM (55 L)
6. extractionthe product was extracted into EtOAc (2×55 L)
7. filtrationThe combined organic phase were filtered
8. customto remove solids
9. customby azeotroping with toluene
10. customdrying to constant weight