Method for preparing 2-amino-n-(2,2,2-trifluoroethyl) acetamide

Patent metadata

Field	Value
Publication number	US-11613516-B2
Application number	US-201916247063-A
Country	US
Kind code	B2
Filing date	Jan 14, 2019
Priority date	Sep 27, 2010
Publication date	Mar 28, 2023
Grant date	Mar 28, 2023

Abstract

Disclosed are methods for preparing compounds of Formula 1 and 1A. The first method utilizes a benzyl carbamate amine protecting group and an intermediate of Formula 4. The second method utilizes a tert-butyl carbamate amine protecting group and an intermediate of Formula 7. The third method utilizes a dibenzyl amine protecting group.

Also disclosed is a compound, phenylmethyl N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]carbamate (a compound of Formula 4).
Further disclosed is a method for preparing a compound of Formula 14 from a compound of Formula 15 and a compound of Formula 1 or 1A.

First claim

What is claimed is:

1. A method for preparing a compound of Formula 14

comprising contacting in a polar aprotic water miscible solvent for 0.5 to 2 hours a compound of Formula 15

with N, N′-carbonyldiimidazole to form an intermediate of Formula 16

and carbon dioxide and imidazole, then directly treating the intermediate of Formula 16 with a compound of Formula 1A by adding a compound of Formula 1A

wherein X is Cl, Br, CF 3 CO 2 , CH 3 SO 3 , (SO 4 ) 1/2 or (PO 4 ) 1/3 and the compound of Formula 1A reacts with the intermediate of Formula 16 to produce the compound of Formula 14, and wherein after completion of reaction of the compound of Formula 1A with the intermediate of formula 16 to produce the compound of Formula 14, adding an aqueous mineral acid to the compound of Formula 14 and then adjusting to pH 9-10 with a base.

2. The method of claim 1 wherein the polar aprotic water miscible solvent comprises acetonitrile, tetrahydrofuran or dioxane.

3. The method of claim 1 wherein the compound of Formula 1A is added as a solid or a solution in the polar aprotic water miscible solvent.

4. The method of claim 1 further comprising the step of adding water to hydrolyze any excess N, N′-carbonyldiimidazole prior to treating the intermediate of Formula 16 with the compound of Formula 1A, wherein the compound of Formula 1A is then added to the mixture as a solution or slurry in water.

5. The method of claim 1 wherein the compound of Formula 1A is contacted with the intermediate of Formula 16 in the presence of an additional base.

6. The method of claim 5 wherein the additional base is triethylamine or diisopropylethylamine.

7. The method of claim 3 wherein the polar aprotic water miscible solvent comprises acetonitrile, tetrahydrofuran or dioxane.

8. The method of claim 1 wherein:
molar ratio of N, N′-carbonyldiimidazole to the compound of Formula 15 is from about 0.95 to about 1.15:
molar ratio of the compound of Formula 1A to the compound of Formula 15 is from about 1.00 to about 1.15;
the compound of Formula 15 and the N, N′-carbonyldiimidazole are contacted at a temperature of between 20° C. and 45° C.; and
the compound of Formula 1A is added at a temperature of between 20° C. and 45° C.

9. The method of claim 8 wherein:
the molar ratio of N, N′-carbonyldiimidazole to the compound of Formula 15 is about 0.97:
the molar ratio of the compound of Formula 1A to the compound of Formula 15 is about 1.05;
the compound of Formula 15 and the N, N′-carbonyldiimidazole are contacted at a temperature of about 35° C.; and
the compound of Formula 1A is added at a temperature of about 35° C.

10. The method of claim 1 wherein X is Cl.

11. The method of claim 4 wherein molar ratio of N, N′-carbonyldiimidazole to the compound of Formula 15 is from about 0.95 to about 1.15, molar ratio of the compound of Formula 1A to the compound of Formula 15 is from about 1.00 to about 1.15, the compound of Formula 15 and the N, N′-carbonyldiimidazole are contacted at a temperature of between 20° C. and 45° C. and the compound of Formula 1A is added at a temperature of between 20° C. and 45° C.

12. The method of claim 11 wherein the polar aprotic water miscible solvent comprises acetonitrile and X is Cl.

13. The method of claim 4 wherein X is Cl.

14. The method of claim 11 wherein the polar aprotic water miscible solvent comprises acetonitrile, tetrahydrofuran or dioxane.

15. The method of claim 4 wherein the compound of Formula 1A is contacted with the intermediate of Formula 16 in the presence of an additional base.

16. The method of claim 15 wherein the additional base is triethylamine or diisopropylethylamine.

17. The method of claim 1 wherein mineral acid is hydrochloric acid and the base is sodium hydroxide or sodium carbonate.

18. The method of claim 1 wherein formation of the intermediate of Formula 16 is monitored by evolution of carbon dioxide gas.

19. The method of claim 4 wherein X is (SO 4 ) 1/2 .

Assignees

• Du Pont

Inventors

• Bruening Joerg

Classifications

• C07C237/06

  having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms · CPC title

• C07C231/12 Primary

  by reactions not involving the formation of carboxamide groups · CPC title

• C07C231/14

  by formation of carboxamide groups together with reactions not involving the carboxamide groups · CPC title

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title

• C07C237/22

  having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated (peptides C07K) · CPC title