METHOD OF PRODUCING INTERMEDIATE COMPOUNDS FOR PREPARING NEP INHIBITORS Russian patent published in 2016 - IPC C07C227/16 C07C229/34 C07C271/22 C07C269/06 

FIELD: chemistry.

SUBSTANCE: compounds (2) and (3a) are intermediate compounds for producing an ethyl ester of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid or salt thereof, which are a NEP (neutral endopeptidase) inhibitor. Method of producing a compound of formula (3a)

,

where R1 and R2 are independently from each other hydrogen or a group which protects nitrogen, selected from C₁-C₆alkoxycarbonyl; and R3 is a carboxyl group -COOH, or salt thereof, involves reaction of compound of formula (1a) or salt thereof, where R1, R2 and R3 have values given above, with a transition metal catalyst containing ruthenium (Ru), rhodium (Rh), palladium (Pd) or Platinum (Pt) in presence of a base selected from amine, alkali metal carbonate, alkali-earth metal carbonate, alkali metal bicarbonate, alkali metal hydroxide, alkali-earth metal hydroxide. Preferred catalyst is a Pd(PPh₃)₄. Obtained compound (3a) is used for conversion into a compound of formula (2)

intended for producing an ethyl ester of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl-butyric acid or salt thereof. Compounds, where R1 is hydrogen; R2 is a BOC; and R3 is a carboxyl group -COOH, are preferably produced and used.

EFFECT: invention relates to a novel method of producing a compound of formula (3a) or salt thereof, as well as to use of a compound of formula (3a) to obtain a compound of formula (2).

6 cl, 1 ex