Method for the preparation of erythro vicinyl amino-alcohols

Abstract

The present invention is concerned with the preparation of erythro N-substituted vicinal aminoalcohol derivatives from hydroxyl-protected cyanohydrin derivatives by successive Grignard reaction, transimination using a primary amine, reduction of the resulting imine and removal of the hydroxyl-protecting group. The products are obtained either as a racemate or in an optically pure form, depending upon the stereochemical composition of the cyanohydrin derivatives.

We claim: 
     
       1. Method for the preparation of an erythro N-substituted vicinal amino-alcohol derivative of formula 1 ##STR7## wherein P is a group protecting the hydroxyl group; R is a monocyclic or bicyclic aryl or heteroaryl group substituted with one or more groups X, wherein X is a hydroxy, alkoxy(1-5C), alkyl(1-5C)carbonyloxy, amino, alkyl(1-5C)carbonylamino, alkyl(1-5C)sulphonylamino, nitro, alkyl(1-5C)sulphonyl, alkyl(1-5C)carbonyl, halogen, cyano, alkyl(1-5C), cycloalkyl(5-12C), or a cyclic group annelated with the aryl group or heteroaryl group, or wherein R is a saturated or unsaturated straight or branched alkyl group having 1-30 C-atoms which may be substituted with halogen, alkoxy(1-5C), alkylthio(1-5C), phenyl or phenoxy optionally substituted with one or more groups X, and   R 1  and R 2  independently of each other are alkyl, alkenyl (2-8C), or phenyl or aralkyl(7-10C), optionally substituted with a group X by reacting a hydroxyl-protected cyanohydrin derivative of formula 2 ##STR8## with a Grignard reagent of formula 3   R.sub.1 --Mg--Hal                                          (3)     yielding a Grignard reacted compound, followed by a novel transimination reaction using a primary amine of formula 4     R.sub.2 --NH.sub.2                                         ( 4)     and reduction of the resulting N-substituted imine, wherein P, R, R 1  and R 2  have the abovementioned meanings and Hal is a halogen atom.     
     
     
       2. Method according to claim 1 wherein use is made of one of the .[.enatiomers.]. .Iadd.enantiomers .Iaddend.of the compound of formula 2 thereby yielding an optically pure erythro derivative of the compound according to formula 1. 
     
     
       3. Method for the preparation of a compound of formula 8 ##STR9## by using the method according to claim 1 or 2 and subsequently removing the hydroxyl-protecting group P of the compound of formula 1, wherein P, R, R 1 , and R2 have the abovementioned meanings. .Iadd. 
     
     
       4.  Method for the preparation of an erythro N-substituted vicinal amino-alcohol derivative of formula 1 ##STR10## wherein P is a group protecting the hydroxyl group; R is an unsubstituted monocyclic or bicyclic aryl or heteroaryl group or a cyclic group annelated with the aryl group or heteroaryl group, and   R 1  and R 2  independently of each other are alkyl, alkenyl (2-8C), or phenyl or aralkyl(7-10C), optionally substituted with a group X by reacting a hydroxyl-protected cyanohydrin derivative of formula 2 ##STR11## with a Grignard reagent of formula 3   R.sub.1 --Mg--Hal                                          (3)     yielding a Grignard reacted compound, followed by a novel transimination reaction using a primary amine of formula 4     R.sub.2 --NH.sub.2                                         ( 4)     and reduction of the resulting N-substituted imine, wherein P, R, R 1  and R 2  have the abovementioned meanings and Hal is a halogen atom. .Iaddend. .Iadd.     
     
     
       5.  Method according to claim 4 wherein use is made of one of the enantiomers of the compound of formula 2 thereby yielding an optically pure erythro derivative of the compound according to formula 1. .Iaddend. .Iadd.6. Method for the preparation of a compound of formula 8 ##STR12## by using the method according to claim 4 or 5 and subsequently removing the hydroxyl-protecting group P of the compound of formula 1, wherein P, R, R 1 , and R 2  have the abovementioned meanings. .Iaddend.