盐酸缬更昔洛韦的合成工艺改进

Improvement of synthetic technology of valganciclovir hydrochloride

目的盐酸缬更昔洛韦的合成工艺改进。方法以更昔洛韦为原料,经乙酰基保护单羟基制得O-单乙酰更昔洛韦,与Cbz-L-缬氨酸经缩合,再经盐酸脱乙酰基得更昔洛韦-Cbz-L-单缬氨酸酯,酸化后在连续流反应器中催化氢化脱苄氧羰基得盐酸缬更昔洛韦粗品,粗品在异丙醇/水(2:1,V/V)中重结晶得到盐酸缬更昔洛韦。结果工艺改进后的操作更加简便安全,可以实现长时间稳定和安全的连续流生产及后处理,目标产品1的收率和纯度得到提高,总收率48.8%,纯度99.4%。结论为盐酸缬更昔洛韦的合成提供了一种较新的方法,生产成本得以降低。

Objective To improve the synthesis process of valganciclovir hydrochloride.Methods Valganciclovir hydrochloride was synthesized from ganciclovir by protection with acetyl to give O-monoacylganciclovir,which was subjected to condensation with Cbz-L-valine and deacetylated hydrochloride to obtain ganciclovir-Cbz-L-monovaline ester.After ganciclovir-Cbz-L-monovaline was acidified,hydrogenation of debenzyloxycarbonyl in a continuous flow reactor was catalyzed to obtain valganciclovir hydrochloride crude product,and the crude product was recrystallized in isopropanol/water(2:1)to obtain valganciclovir hydrochloride.Result The improved process made the operation more convenient and safe,enabling long-term stable and safe continuous production and post-treatment.The yield and purity of target product 1 had been improved,with a total yield of 48.8%and a purity of 99.4%.Conclusion This research provided a relatively new method for the synthesis of valganciclovir hydrochloride,reducing production costs.