“One-Pot” Synthesis of Molnupiravir from Cytidine

Abstract

A one-pot process for preparing molnupiravir from cytidine was developed. The advantages of this synthesis were as follows: (1) The presence of N,N-dimethylformamide dimethyl acetal (DMF-DMA) facilitated the selective protection of 2′,3′-dihydroxyls and amino of cytidine, which eliminated the negative impact of these groups on the following isobutyrylation at 5′-hydroxyl. (2) Degradations of the product in the deprotection stage were avoided since a mild condition was used. (3) The achievement of deprotection and hydroxyamination in one single step improved the synthetic efficiency. (4) Molnupiravir with high purity (purity up to 99.7% analyzed by high-performance liquid chromatography (HPLC)) was obtained in a yield of 63% through crystallization.