HUP0500622A2 - New intermediates and process for producing them - Google Patents

Abstract

Preparation of enantiomers of aryl-isopropanol derivatives involves enantioselective acylating the corresponding racemic alcohol in an enzyme catalyzed reaction; acylating the enantiomeric aryl-isopropanol with a dicarboxylic acid derivative in presence of an acylated enantiomer; converting the dicarboxylic acid derivative into a salt; separating two phases and working up to obtain the individual enantiomeric derivatives. Preparation of enantiomers of aryl-isopropanol derivatives of formula (I) involves enantioselective acylating the corresponding racemic alcohol of formula (Ia) in an enzyme catalyzed reaction; acylating the enantiomeric aryl-isopropanol of formula (Ib) which remained unchanged under the conditions of the enzyme-catalyzed reaction with a dicarboxylic acid derivative in the presence of an acylated enantiomer of formula (Ic) formed in the enzyme catalyzed reaction (where at least one of R1 and R2 is other than H); converting the dicarboxylic acid derivative of formula (Id) into a salt by using an aqueous base in the presence of a water-insoluble solvent; separating the aqueous phase which contains the dicarboxylic acid derivative of formula (Id) from the organic phase which contains the acylated enantiomeric derivative of formula (Ic); working up both phases to obtain the individual enantiomeric derivatives; and optionally converting the enantiomeric derivatives into other derivatives and/or purifying. R3=H or 1-4C acyl (optionally substituted with R5 further substituted with carboxy group); R1 and R2=H, 1-4C alkyl, 1-4C alkoxy, aryloxy, aralkoxy, trifluoromethyl, cyano or halogen; R1R2=methylenedioxy; R4=1-4C alkyl; R5=alkyl, alkenyl or aryl (all optionally substituted). An independent claim is included for new racemic-isopropanol derivatives of formula (I), and salts of their racemic or optically active enantiomers formed with optically active bases with the exception of salts formed with optically active brucine as base and compounds of formula (I) (where R3 is phthalyl, one of R1 and R2 is methoxy attached to position to 3 of the phenyl ring and the other is H or methoxy attached to position 4 of the phenyl ring). The chiral carbon atom is of (R)- or (S)-configuration. Provided that: (a) when chiral carbon atom is of (S)-configuration, and R3 is H, then at least one of R1 and R2 is other than H; if R1 and R2 stand for alkoxy, one of the substituents is attached to position 2 of the phenyl ring; if R1R2 form methylenedioxy the phenyl ring form 1-benzo[1,3]dioxol-4-yl; if one of symbols R1 and R2 is cyano is attached to position 2, the other group is other than H or methoxy attached to position 3; or if one of symbols of R1 and R2 is H, the other is different from methoxy attached to position 2 or 3; (b) when chiral carbon atom is of (R)-configuration, and R3 is H, then at least one of R1 and R2 is other than H; if R1 and R2 stand for 1-4C alkoxy, one of the alkoxy group is attached to position 2 of the phenyl ring; if R1R2 form methylenedioxy the phenyl ring form 1-benzo[1,3]dioxol-4-yl; if one of R1 and R2 stands for trifluoromethyl attached to position 3 or fluorine attached to position 4, the other is other than H; (c) when chiral carbon atom is of (S)-configuration, and R3 is 1-4C acyl, then at least one of R1 and R2 is other than H; if R3 is acetyl and at least one of R1 and R2 is H, the substituent attached to position 4 of the phenyl ring is other than methoxy; (d) when chiral carbon atom is of (R)-configuration, and R3 is 1-4C acyl, then at least one of R1 and R2 is other than H; if R3 is acetyl and R1R2 form methylenedioxy, the group together with the phenyl ring form 1-benzo[l,3]dioxole-4-yl; (e) if R3 is phthalyl, one of symbols R1 and R2 represents methoxy attached to position 3 of the phenyl ring and the other is different from H or methoxy attached to position 4 of the phenyl ring. [Image] [Image].