Process for preparing β-amino-α-hydroxycarboxamides

1. A process for preparing enantiomerically enriched compounds of general formula (I)

in which

R 1 , R 2 , R 3 , R 4 , R 5 are each independently (C 1 -C 8 )-alkyl, HO—(C 1 -C 8 )-alkyl, (C 2 -C 8 )-alkoxyalkyl, (C 6 -C 18 )-aryl, (C 7 - 19 )-aralkyl, (C 3 -C 18 )-heteroaryl, (C 4 -C 19 )-heteroaralkyl, (C 1 -C 8 )-alkyl-(C 6 -C 18 )-aryl, (C 1 -C 8 )-alkyl-(C 3 -C 18 )-heteroaryl, (C 3 -C 8 )-cycloalkyl, (C 1 -C 8 )-alkyl-(C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 8 )-alkyl, or

R 4 and R 5 and/or R 2 and R 3 together form a (C 2 -C 8 )-alkylene bridge,

where R 1 , R 2 , R 3 , R 4 may additionally be H and

with the proviso that R 1 is not phenyl when R 4 and/or R 5 =H,

said process comprising:

a) reacting epoxycarboxamides of general formula (II)

in which R 1 , R 4 , R 5 are each as defined above,

with ammonia or amines of the general formula (III)

in which R 2 , R 3 are each as defined above; wherein enantiomerically enriched compounds of general formula (I) are prepared using enantiomerically enriched compounds of formula (II); or as a second step

b) enantioselectively crystallizing the salts of racemic diastereomerically enriched compounds of formula (I) using a chiral organic acid;

and wherein one or more of the following conditions apply:

i) R 1 is a (C 1 -C 8 )-alkyl;

ii) R 4 is H;

iii) R 5 is a (C 1 -C 8 )-alkyl-(C 3 -C 8 )-cycloalkyl;

iv) R 5 is cyclopropyl.

2. The process of claim 1 , wherein the reaction between said epoxycarboxamides and said ammonia or amines is performed at a temperature of 0-200° C. at the autogenous pressure.

3. The process of claim 2 , wherein the reaction between said epoxycarboxamides and said ammonia or amines is performed at a temperature of 20-150° C. at the autogenous pressure.

4. The process of claim 2 , wherein the reaction between said epoxycarboxamides and said ammonia or amines is performed at a temperature of 50-100° C. at the autogenous pressure.

5. The process of claim 2 , wherein the reaction between said epoxycarboxamides and said ammonia or amines is performed in a solvent selected from the group consisting of: water, and aqueous or nonaqueous organic solvents.

6. The process of claim 1 , wherein the reaction between said epoxycarboxamides and said ammonia or amines is performed at a temperature of 0-200° C. at the autogenous pressure.

7. The process of claim 6 , wherein the reaction between said epoxycarboxamides and said ammonia or amines is performed at a temperature of 20-150° C. at the autogenous pressure.

8. The process of claim 6 , wherein the reaction between said epoxycarboxamides and said ammonia or amines is performed at a temperature of 50-100° C. at the autogenous pressure.

9. The process of claim 6 , wherein the reaction between said epoxycarboxamides and said ammonia or amines is performed in a solvent selected from the group consisting of: water, and aqueous or nonaqueous organic solvents.

10. The process of claim 1 , wherein R 1 is a (C 1 -C 8 )-alkyl.

11. The process of claim 1 , wherein R 4 is H.

12. The process of claim 1 , wherein R 5 is (C 1 -C 8 )-alkyl-(C 3 -C 8 ) cycloalkyl.

13. The process of claim 12 , wherein R 1 is a (C 1 -C 8 )-alkyl.

14. The process of claim 13 , wherein R 2 and R 3 are H.

15. The process of claim 14 , wherein R 4 is H.

16. The process of claim 1 , wherein R 5 is cyclopropyl.

17. The process of claim 16 , wherein R 1 is a (C 1 -C 8 )-alkyl.

18. The process of claim 17 , wherein R 2 , R 3 and R 4 are H.

19. The process of claim 1 , wherein said chiral organic acid is an N-acylamino acid, a sulphonic acid or an aminodicarboxylic acid.

20. The process of claim 1 , wherein said chiral organic acid is selected from the group consisting of: mandelic acid, dibenzoyltartaric acid, ditolyltartaric acid, lactic acid, acetyl-L-phenylalanine and camphorsulphonic acid.

21. The process of claim 1 , wherein said chiral organic acid is benzyloxycarbonyl-L-phenylalanine.