Method for the preparation of erythro vicinyl amino-alcohols
AssigneeDuphar International Research B.V.
InventorsJohannes Brussee, Arne van der Gen, Cornelis G. Kruse
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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.
Claims6
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.sub.1 and R.sub.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.sub.1 and R.sub.2 have the abovementioned meanings and Hal is a halogen atom.
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.sub.1 and R.sub.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.sub.1 and R.sub.2 have the abovementioned meanings and Hal is a halogen atom.
Dependencies are inferred from the claim text.