Salts of carnitine derivatives and methods of production

Patent metadata

Field	Value
Publication number	US-2017158612-A1
Application number	US-201715438516-A
Country	US
Kind code	A1
Filing date	Feb 21, 2017
Priority date	Dec 16, 2013
Publication date	Jun 8, 2017
Grant date	—

Abstract

Disclosed are salts, such as nitrates, of acetyl-L-carnitine and propionyl-L-carnitine and methods of making the compounds.

First claim

1 . A method of producing acetyl-L-carnitine nitrate comprising:
reacting L-carnitine with acetic anhydride to produce acetyl-L-carnitine free base; isolating the acetyl-L-carnitine free base; reacting the acetyl-L-carnitine free base with nitric acid to produce acetyl-L-carnitine nitrate; and isolating the acetyl-L-carnitine nitrate.

2 . The method of claim 1 , wherein the molar ratio of acetic anhydride to L-carnitine is about 1:1 to 3:1.

3 . The method of claim 1 , wherein the molar ratio of nitric acid to acetyl-L-carnitine free base is about 1:1 to 1.5:1.

4 . The method of claim 1 , wherein reacting L-carnitine with acetic anhydride to produce acetyl-L-carnitine free base comprises dissolving the L-carnitine in acetic acid, and wherein the reaction between L-carnitine and acetic anhydride occurs at a temperature of between 30° C. and 80° C.

5 . The method of claim 4 , wherein the ratio of acetic acid to L-carnitine is about 0.65 g to 3 g acetic acid for every gram of L-carnitine.

6 . The method of claim 4 , wherein the reaction between L-carnitine and acetic anhydride occurs for 3 to 12 hours.

7 . The method of claim 1 , wherein isolating the acetyl-L-carnitine free base comprises:
distilling the reaction of L-carnitine free base and acetyl anhydride to remove the other products of the reaction; washing the acetyl-L-carnitine free base with acetone; and crystallizing the acetyl-L-carnitine free base.

8 . The method of claim 7 , wherein distilling the reaction of L-carnitine and acetic anhydride occurs at reduced pressure.

9 . The method of claim 8 , wherein distilling the reaction of L-carnitine and acetic anhydride occurs in a vacuum.

10 . The method of claim 8 , wherein washing the acetyl-L-carnitine free base with acetone comprises using an amount of acetone by grams that is two to five times the amount L-carnitine by grams.

11 . The method of claim 8 , wherein crystallizing the acetyl-L-carnitine free base comprises cooling the acetyl-L-carnitine free base to below 5° C.

12 . The method of claim 11 , wherein crystallizing the acetyl-L-carnitine free base further comprises maintaining the acetyl-L-carnitine free base at between 0° C. and 5° C. for at least 2 hours.

13 . The method of claim 1 , wherein reacting the acetyl-L-carnitine free base with nitric acid to produce acetyl-L-carnitine nitrate comprises dissolving the acetyl-L-carnitine in acetic acid, wherein the reaction between L-carnitine and acetic anhydride occurs at a temperature of between 30° C. and 80° C.

14 . The method of claim 13 , wherein the ratio of acetic acid to acetyl L-carnitine free base is about 0.8 g to 3 g acetic acid for every gram of acetyl-L-carnitine free base.

15 . The method of claim 13 , wherein the reaction between the acetyl-L-carnitine free base and nitric acid occurs for about 2 to 5 hours.

16 . The method of claim 1 , wherein isolating the acetyl-L-carnitine nitrate comprises:
distilling the reaction of acetyl-L-carnitine free base and nitric acid to remove the other products of the reaction; washing the acetyl-L-carnitine nitrate with acetone; and crystallizing the acetyl-L-carnitine nitrate.

17 . The method of claim 16 , wherein washing the acetyl-L-carnitine nitrate with acetone comprises using an amount of acetone by weight that is two to five times the amount acetyl-L-carnitine free base by weight.

18 . The method of claim 16 , wherein crystallizing the acetyl-L-carnitine nitrate comprises cooling the acetyl-L-carnitine nitrate to below 5° C.

19 . The method of claim 18 , wherein crystallizing acetyl-L-carnitine nitrate further comprises maintaining the acetyl-L-carnitine nitrate at between 0° C. and 5° C. for at least 2 hours.

Assignees

• Thermolife Int Llc

Inventors

• Kramer Ronald
• Nikolaidis Alexander

Classifications

• C07C227/42

  Crystallisation · CPC title

• C07C229/22 Primary

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

• C07C227/16 Primary

  by reactions not involving the amino or carboxyl groups · CPC title