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  • Kilo-scale synthesis process for 2'-O-(2-methoxyethyl)-pyrimidine derivatives.

Kilo-scale synthesis process for 2'-O-(2-methoxyethyl)-pyrimidine derivatives.

Nucleosides, nucleotides & nucleic acids (2005-10-27)
Bruce S Ross, Quanlai Song, Mingming Han
ABSTRACT

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-methaxyethyl)-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.

MATERIALS
Product Number
Brand
Product Description

Supelco
2,6-Lutidine, analytical standard
Sigma-Aldrich
5-Methyluridine, 97%
Sigma-Aldrich
2,6-Lutidine, ReagentPlus®, 98%
Sigma-Aldrich
2,6-Lutidine
Sigma-Aldrich
5-Methylcytidine, ≥99%
Sigma-Aldrich
2,6-Dimethylpyridine, ≥99%