We describe an improved process to produce 2′-O-(2-methoxyethyl)-pyrimidines. Starting with commercially available O-2,2′-anhydro-5-methyluridine and tris-(2-methoxyethyl)borate, we modified the ring-opening reaction conditions and changed to a continuous extraction purification method to give 2′-O-(2-methoxyethyl)-5-methyluridine. The dimethoxytritylation 5′/3′ ratios and yield were improved by the use of 2,6-lutidine as the base. Conditions to convert to the 5-methylcytidine analog and its isolation by crystallization were optimized. Final benzoylation was improved by developing a method to selectively hydrolyze benzoyl ester impurities.

中文翻译：

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2'-O-(2-甲氧基乙基)-嘧啶衍生物的千级合成工艺

我们描述了一种生产 2'-O-(2-甲氧基乙基)-嘧啶的改进方法。我们以市售的O-2,2'-脱水-5-甲基尿苷和三-(2-甲氧基乙基)硼酸盐为原料，修改开环反应条件，改为连续萃取纯化的方法，得到2'-O-( 2-甲氧基乙基)-5-甲基尿苷。通过使用 2,6-二甲基吡啶作为碱提高了二甲氧基三苯甲基化 5'/3' 比率和产率。优化了转化为 5-甲基胞苷类似物的条件及其通过结晶的分离。通过开发一种选择性水解苯甲酸酯杂质的方法来改善最终的苯甲酰化。