Delmar Chemicals Inc.

Shire Biochem, Inc.

Gregory Bydlinski

Alex Cimpoia

Yuan Wang

Qing Yu

Lu Wei Liu

David D C Quan

Zhihong (Nancy) Zhou

Sylvain Harper

H&eacute;rika Marrugo

The present invention relates to a process conducted in a single reaction vessel for producing a dioxolane nucleoside analogue of formula I or a pharmaceutically acceptable salt thereof; the process comprising the steps of adding a Lewis acid, a silylating agent and a non-silylated purine or pyrimidine base or an analogue thereof to a dioxolane of formula II. The invention also provides a process for producing a dioxolane compound of formula III; by reacting a dioxolane compound of formula IV in a suitable solvent in the presence of DIB and I, using a suitable source of energy.

Process for producing dioxolane nucleoside analogues

A process for the preparation of highly pure 1-(mercaptomethyl)-cyclopropaneacetic acid is described. Treatment of 1-(hydroxymethyl)-cyclopropaneacetonitrile with an acid provides the corresponding imino ester and/or halo-amide, which when reacted with thiourea provide the corresponding amide-isothiuronium salt. Hydrolysis of the amide-isothiuronium salt followed by an in situ oxidation allows the facile isolation and purification of 1-&lsqb;1 -(carboxymethyl)-cyclopropanemethyldisulfanylmethyl&rsqb;-cyclopropaneacetic acid (also known as 1-(mercaptomethyl)-cyclopropaneacetic acid disulfide). Reduction of the 1-(mercaptomethyl)-cyclopropaneacetic acid disulfide under mild conditions provides the 1-(mercaptomethyl)-cyclopropaneacetic acid with high purity.

Process for the preparation of 1-(mercaptomethyl)-cyclopropaneacetic acid

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Montreal, Canada

Gregory Bydlinski