# US 7,612,237 B2 · Process for preparing β-amino-α-hydroxycarboxamides

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- Number: US 7,612,237 B2
- Document ID: US7612237B2
- Status: Granted
- Kind: B2
- Application number: 11/819,964
- Filed: 2007-06-29
- Published: 2008-01-17
- Granted: 2009-11-03
- Earliest claimed: 2006-07-04
- Assignees: Degussa AG
- Inventors: Günter Knaup
- Web page: https://patentgrep.com/patent/US7612237B2

## CPC

- C07D 303/48: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. ester or nitrile radicals
- C07C 231/12: by reactions not involving the formation of carboxamide groups
- C07C 231/20: by separation of optical isomers
- C07C 237/04: the carbon skeleton being acyclic and saturated
- C07C 271/22: to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
- C07C 2601/02: with a three-membered ring
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

The present invention is directed to a process for preparing β-amino-α-hydroxycarboxamides. The process works with epoxycarboxamides of the formula 2 which are reacted with ammonia or other amines.

## Claims

### Claim 1

A process for preparing enantiomerically enriched compounds of general formula (I)
in which
R1, R2, R3, R4, R5 are each independently (C1-C8)-alkyl, HO—(C1-C8)-alkyl, (C2-C8)-alkoxyalkyl, (C6-C18)-aryl, (C7-19)-aralkyl, (C3-C18)-heteroaryl, (C4-C19)-heteroaralkyl, (C1-C8)-alkyl-(C6-C18)-aryl, (C1-C8)-alkyl-(C3-C18)-heteroaryl, (C3-C8)-cycloalkyl, (C1-C8)-alkyl-(C3-C8)-cycloalkyl, (C3-C8)-cycloalkyl-(C1-C8)-alkyl, or
R4 and R5 and/or R2 and R3 together form a (C2-C8)-alkylene bridge,
where R1, R2, R3, R4 may additionally be H and
with the proviso that R1 is not phenyl when R4 and/or R5=H,
said process comprising:
a) reacting epoxycarboxamides of general formula (II)
in which R1, R4, R5 are each as defined above,
with ammonia or amines of the general formula (III)
in which R2, R3 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) R1 is a (C1-C8)-alkyl;
ii) R4 is H;
iii) R5 is a (C1-C8)-alkyl-(C3-C8)-cycloalkyl;
iv) R5 is cyclopropyl.

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 2)

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.

### Claim 4 (depends on 2)

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.

### Claim 5 (depends on 2)

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.

### Claim 6 (depends on 1)

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.

### Claim 7 (depends on 6)

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.

### Claim 8 (depends on 6)

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.

### Claim 9 (depends on 6)

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.

### Claim 10 (depends on 1)

The process of claim 1, wherein R1 is a (C1-C8)-alkyl.

### Claim 11 (depends on 1)

The process of claim 1, wherein R4 is H.

### Claim 12 (depends on 1)

The process of claim 1, wherein R5 is (C1-C8)-alkyl-(C3-C8) cycloalkyl.

### Claim 13 (depends on 12)

The process of claim 12, wherein R1 is a (C1-C8)-alkyl.

### Claim 14 (depends on 13)

The process of claim 13, wherein R2 and R3 are H.

### Claim 15 (depends on 14)

The process of claim 14, wherein R4 is H.

### Claim 16 (depends on 1)

The process of claim 1, wherein R5 is cyclopropyl.

### Claim 17 (depends on 16)

The process of claim 16, wherein R1 is a (C1-C8)-alkyl.

### Claim 18 (depends on 17)

The process of claim 17, wherein R2, R3 and R4 are H.

### Claim 19 (depends on 1)

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

### Claim 20 (depends on 1)

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.

### Claim 21 (depends on 1)

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