Preparation of optically active 3-phenylpropionic acid derivatives, used for preparing halo-phenyl compounds, comprises hydrogenating cis-isomer mixture of phenyl compound, crystallizing enantiomer mixture and isolating solid material

摘要

Preparation of an optically active 3-phenylpropionic acid derivative (I) comprises: (a) an enantioselective hydrogenation of a cis-isomer or cis/trans-isomer mixture of a phenyl compound (II) in the presence of a chiral hydrogenation catalyst to give an enantiomer enriched enantiomer mixture; (b) crystallization of the enantiomer enriched enantiomer mixture by supplementation of a basic salt former in a solvent and isolating the stereoisomer enriched solid material; and (c) optionally isolation of the protonated isomer or a substitutional cation. Preparation of an optically active 3-phenylpropionic acid derivative of formula (I) comprises: (a) an enantioselective hydrogenation of a cis-isomer or cis/trans-isomer mixture of a phenyl compound of formula (II) in the presence of a chiral hydrogenation catalyst to give an enantiomer enriched enantiomer mixture; (b) crystallization of the enantiomer enriched enantiomer mixture by supplementation of a basic salt former in a solvent and isolating the stereoisomer enriched solid material; and (c) optionally isolation of the protonated isomer or a substitutional cation. R 1-R 4H, 1-6C alkyl, halo-1-6C alkyl, OH-1-6C alkyl, 1-6C alkoxy, OH-1-6C alkoxy, 1-6C alkoxy-1-6C alkyl, OH-1-6C alkoxy-1-6C alkyl, 1-6C alkoxy-1-6C alkoxy or OH-1-6C alkoxy-1-6C alkoxy; R 51-6C alkyl, 5-8C cycloalkyl, phenyl or benzyl; and A : H or cationic equivalent. Independent claims are also included for: (1) the preparation of optically active halo-phenyl compound of formula (III), which comprises protonating (I) in to an acid; reducing the acids or the metal salts to give an alcohol compound of formula (IV); and halodehydroxylating (IV); and (2) an optically active compound 3-phenylpropionic acid derivative (I). Hal : Cl, Br or I. [Image] [Image].