US 2014/0228574 A1 · Processes and Intermediates for Preparing a Macrocyclic Protease Inhibitor of HCV

Abstract

Disclosed is a process for the preparation of a cinchonidine salt of formula (IV) via an aqueous solution of a racemic 4-hydroxy-1,2-cyclopentanedicarboxylic acid, which is subjected to cyclization without removing water, by the addition of a water-miscible organic solvent to the aqueous solution and, again without removing water, adding cinchonidine to the aqueous-organic solvent solution so as to obtain the cinchonidine salt of the lactone acid. The cinchonidine salt is allowd to crystallize so as to obtain the enantiomerically purified crystalline lactone acid cinchonidine salt (IV). The enantiomerically pure salt is an intermediate in the synthesis of HCV inhibitor compound of formula (I).

Claims13

Dependent claims

A process for the preparation of a cinchonidine salt of formula (IV) comprising the steps of:

(a) subjecting 4-oxo-1,2-cyclopentanedicarboxylic acid (V) to reduction in an aqueous environment, thus providing an aqueous solution of racemic 4-hydroxy-1,2-cyclopentanedicarboxylic acid (VI);
(b) adding an organic solvent (e.g. water-miscible organic solvent) to the aqueous solution obtained in (a);
(c) subjecting the racemic hydroxyacid (VI) to cyclization so as to obtain an aqueous-organic solvent solution of the corresponding racemic lactone acid (II);
(d) adding cinchonidine to the aqueous-organic solvent solution obtained in (c) so as to obtain the cinchonidine salt (III) of the lactone acid;
(e) allowing the cinchonidine salt to crystallize so as to obtain the enantiomerically purified crystalline lactone acid cinchonidine salt (IV), the numbered formulae herein being as follows:

2 more elements

Dependencies are inferred from the claim text.

Processes and Intermediates for Preparing a Macrocyclic Protease Inhibitor of HCV

Life of this patent

Processes and Intermediates for Preparing a Macrocyclic Protease Inhibitor of HCV

Life of this patent

Abstract

Claims13