FIELD: chemistry.
SUBSTANCE: invention relates to a process for the preparation of enantiomerically and diastereomerically enriched cyclobutane amines with formula (VII). The method involves (a) reducing the nitrile moiety of a compound with formula (I) to an aldehyde, wherein the reduction of the nitrile moiety of a compound with formula (I) is carried out by partial hydrogenation to the relevant intermediate imine using H2 and a metal catalyst, followed by sequential hydrolysis to produce the compound with formula (II). The method then comprises (b) reacting a compound with formula (II) in the presence of a Lewis acid to obtain a compound with formula (III). The process then comprises (c) reacting a compound with formula (III) with an ammonium salt and H2 in the presence of a chiral transition metal catalyst to produce an enantiomerically and diastereomerically enriched amine with formula (IV) and then reacting an amine with formula (IV) with a compound with formula (X) to form an enantiomerically and diastereomerically enriched amide with formula (VII). In these formulas, A is selected from aryl and heteroaryl, where aryl and heteroaryl are unsubstituted or substituted with one or more substituents independently selected from halogen, cyano, C1 -C6 alkyl, C1 -C6 haloalkyl, C1 -C6 alkoxy and C1 -C6 haloalkoxy; Y is a suitable leaving group such as OH, OR or halogen, preferably chlorine, R is C1 -C6 alkyl; E is selected from aryl and heteroaryl, where aryl and heteroaryl are unsubstituted or substituted with one or more substituents independently selected from halogen, cyano, C1 -C6 alkyl, C1 -C6 haloalkyl, C1 -C6 alkoxy and C1 -C6 haloalkoxy; * denotes stereocenter; aryl is a mono-, bi- or polycyclic aromatic system with 6-14 carbon atoms in the ring, heteroaryl is 5-7-membered rings with 1-3 identical or different heteroatoms selected from N, O and S. The proposed method allows to improve existing methods for the preparation of enantiomerically and diastereomerically enriched cyclobutanamides with formula (VII).
EFFECT: processes for the preparation of a compound with formula (III) and a process for the preparation of a compound with formula (V).
14 cl, 27 tbl, 213 ex
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