Patent ID: 8329902

Claim:
A process for preparing an optically pure compound of formula (I), wherein R 1 represents hydrogen, R 2 represents phenyl optionally substituted up to 5 times by fluoro, or thiazolyl optionally substituted by one or more substituents which are the same or different, and selected from: fluoro, chloro, bromo, (C 1 -C 3 )-alkyl, (C 1 -C 3 )-alkoxy, amino, and (C 1 -C 3 ) -acylamino, R 3 represents phenyl, optionally substituted by one or more substituents which are the same or different, and selected from: fluoro, chloro, bromo, iodo, hydroxyl, trifluoromethyl, trifluoromethoxy, trifluoromethylsulfonyl, nitro, cyano, carboxy, and methoxycarbonyl, and R 4 represents a group represented by formula —OR 11 , wherein R 11 represents hydrogen, (C 1 -C 3 )-alkenyl or (C 1 -C 4 )-alkyl, wherein the (C 1 -C 3 )-alkenyl and (C 1 -C 4 )-alkyl independently are optionally substituted by halogen, pyridyl, cyano, phenoxy, alkoxy, trifluoroethyl, benzyl or a group represented by formula —NR 15 R 16 , wherein R 15 and R 16 , the same or different, respectively represent hydrogen, benzyl or methyl, or a pharmaceutically acceptable salt thereof, comprising the steps of: 1) reacting an amidine of formula (II) or a salt thereof wherein R 2 is defined as above, with an aldehyde of formula (III) wherein R 3 is defined as above, and a compound of formula (IV) CH 3 COCH 2 CONHCR 12 R 13 R 14 (IV) wherein R 12 , R 13 , R 14 are different and respectively represent a substituent selected from hydrogen, substituted or unsubstituted phenyl, benzyl, or a straight or branched (C 1 -C 3 ) -hydrocarbyl, in the presence or absence of a base or acid, and in a suitable inert solvent, to obtain a compound of formula (V) or reacting a compound of formula (VI) or (VII) wherein R 3 , R 12 , R 13 ,and R 14 are defined as above, with a compound of formula (II), in the presence or absence of a base or acid, at a temperature of 20-150° C., and in a suitable inert solvent, to obtain a compound of formula (V), or reacting a aldehyde of formula (III) with a compound of formula (IV) and an iminoether of formula (VIII) wherein R 2 is defined as above, and R′ is C 1 -C 4 alkyl, in the presence of an ammonium salt, to obtain a compound of formula (V), 2) acylating the compound of formula (V) in a suitable solvent, to obtain a compound of formula (IX) wherein R 1 is (C 1 -C 6 )-acyl, arylacyl or arylsulfonyl, and R 2 , R 3 , R 12 , R 13 and R 14 are defined as above, and 3) the compound of formula (IX) is nitrosylated under an acidic or basic condition in a suitable solvent, and then reacted with sodium alkoxide R 11 ONa to obtain a optically pure compound of formula (I) wherein R 1 , R 2 , R 3 , and R 4 are defined as above.