METHODS AND INTERMEDIATE COMPOUNDS FOR OBTAINING MACROCYCLIC INHIBITORS OF PROTEASE HCV Russian patent published in 2017 - IPC C07C51/487 C07C61/06 C07C69/74 C07C235/40 C07C205/57 C07C215/30 C07C201/12 C07C231/12 C07C255/57 C07D251/28 C07D251/30 C07D309/30 C07D417/04 C07D417/14 C07D491/18 

FIELD: chemistry.

SUBSTANCE: invention relates in particular to an improved process of preparation of (1R, 2R)-4-oxo-1,2-cyclopentanedicarboxylic acid II by resolution of racemic 4-oxo-1,2-cyclopentanedicarboxylic acid (V). This method comprises: a) reacting 4-oxo-1,2-cyclopentanedicarboxylic acid (V) with brucine or (1R, 2S)-(-)- ephedrine to give the bis-brucinic or bis- (1R, 2S) -(-)- ephedrine salt of compound (V), and b) selective precipitation of (1R, 2R)-4-oxo-1,2-cyclopentanedicarboxylic acid bis-brucine or bis- (1R, 2S)-(-)- ephedrine salt II. The bis-brucine or bis (1R, 2S)-(-)- ephedrine salt of (1S, 2S)-4-oxo-1,2-cyclopentanedicarboxylic acid remains in solution; C) the release of acid II by removal of brucine or (1R, 2S)-(-)- ephedrine from the precipitated salt obtained in step (b); which is outlined in the following reaction scheme. .

EFFECT: methods allow the production of large quantities of the active ingredient based on the methods that provide the product in high yield and with a high degree of purity.

22 cl, 41 ex