反应详情

To the toluene solution from Step B at ambient temperature were added methanol (25 L) and n-butylamine (3.13 kg, 42.9 mol). The reaction mixture was aged at 64° C. for 24 to 30 h. The mixture was concentrated to about 9 L, and 9 L of methanol was added. The solution was concentrated to 9 L, and the resulting slurry was aged at 60° C. for 60 min. Toluene (13 L) was added over 1.5 h. The slurry was aged at 60° C. for another 2 h and then allowed to cool to ambient temperature. The solid was filtered and the wet cake was washed with 9 L of 20% methanol in toluene then 9 L of 10% methanol in toluene. The solid was suction dried at ambient temperature under nitrogen to give 1.79 kg (94 wt % pure) of the title nucleoside 4-3 as the toluene solvate.

1. concentrationThe mixture was concentrated to about 9 L, and 9 L of methanol
2. additionwas added
3. concentrationThe solution was concentrated to 9 L
4. waitthe resulting slurry was aged at 60° C. for 60 min
5. additionToluene (13 L) was added over 1.5 h
6. waitThe slurry was aged at 60° C. for another 2 h
7. filtrationThe solid was filtered
8. washthe wet cake was washed with 9 L of 20% methanol in toluene
9. customdried at ambient temperature under nitrogen