Process for the production of carnitine from β-lactones

Patent metadata

Field	Value
Publication number	US-9394238-B2
Application number	US-201414521700-A
Country	US
Kind code	B2
Filing date	Oct 23, 2014
Priority date	Jul 21, 2010
Publication date	Jul 19, 2016
Grant date	Jul 19, 2016

Abstract

The invention relates to a method for the production of L-carnitine, wherein a β-lactone, which is a 4-(halomethyl)oxetane-2-one, is converted into carnitine with trimethylamine (TMA), wherein the β-lactone is not subjected to a basic hydrolysis step before being contacted with the trimethylamine. The invention also relates to a carnitine having a unique impurity profile.

First claim

The invention claimed is:

1. A process for the production of L-carnitine, wherein a β-lactone, which is a 4-(halomethyl)oxetane-2-one, is converted into carnitine with trimethylamine (TMA), wherein the β-lactone is not subjected to a hydrolysis step before being contacted with the trimethylamine.

2. The process of claim 1 , wherein a basic hydrolysis and addition of trimethylamine (TMA) are carried out in one process step.

3. The process of claim 1 , wherein the basic hydrolysis is carried out with a metal hydroxide, preferably sodium hydroxide.

4. The process of claim 3 , wherein the β-lactone is brought into contact with the metal hydroxide and the trimethylamine essentially at the same time.

5. The process of claim 3 , wherein the amount of the metal hydroxide is 1.1 to 1.6 equivalents, preferably 1.2 to 1.4 equivalents, based on the initial amount of β-lactone.

6. The process of claim 3 , wherein the β-lactone is brought into contact with an aqueous solution comprising the metal hydroxide and the trimethylamine.

7. The process of claim 3 , wherein a solution of the β-lactone in an organic solvent is provided and mixed with an aqueous solution comprising TMA and a metal hydroxide.

8. The process of claim 1 , wherein the reaction is carried out at a temperature between −20° C. and 40° C., preferably between 0° C. and 25° C.

9. The process of claim 1 , wherein basic hydrolysis is mediated by the TMA and no additional base is added for basic hydrolysis.

10. The process of claim 1 , wherein the β-lactone is a chiral β-lactone and the carnitine is L-carnitine.

11. The process of claim 1 , comprising an additional step, in which the L-carnitine is purified via a combination of electrodialysis and subsequent recrystallization.

12. The process of claim 1 , comprising a preceding step, in which the β-lactone is obtained in a [2+2] cycloaddition of ketene with an aldehyde X—CH 2 —CHO, wherein X is selected from Cl, Br and I, in the presence of a chiral catalyst.

13. The process of claim 12 , wherein the chiral catalyst is a Lewis acid-Lewis base bifunctional metal catalyst or an organic phosphine catalyst.

14. L-carnitine, characterized by having an amount of hydroxycrotonic acid in the range of 0.5-0.1 wt-% or in the range of 0.5-0.005 wt-%.

15. The process of claim 4 , wherein the amount of the metal hydroxide is 1.1 to 1.6 equivalents, preferably 1.2 to 1.4 equivalents, based on the initial amount of β-lactone.

16. The process of claim 4 , wherein the β-lactone is brought into contact with an aqueous solution comprising the metal hydroxide and the trimethylamine.

17. The process of claim 5 , wherein the β-lactone is brought into contact with an aqueous solution comprising the metal hydroxide and the trimethylamine.

18. The process of claim 6 , wherein a solution of the β-lactone in an organic solvent is provided and mixed with an aqueous solution comprising TMA and a metal hydroxide.

19. The L-carnitine of claim 14 , obtainable by a process according to claim 11 .

Assignees

• Lonza Ag

Inventors

• Hanselmann Paul
• Klegraf Ellen

Classifications

• C07C229/22 Primary

  the carbon skeleton being further substituted by oxygen atoms · CPC title

• C07C227/40

  Separation; Purification · CPC title

• C07D305/12

  Beta-lactones · CPC title

• C07C227/42

  Crystallisation · CPC title

• C07C227/08

  by reaction of ammonia or amines with acids containing functional groups · CPC title