Methods for producing crystalline L-glufosinate ammonium monohydrate

Patent metadata

Field	Value
Publication number	US-12234254-B2
Application number	US-202017603759-A
Country	US
Kind code	B2
Filing date	Apr 15, 2020
Priority date	Apr 16, 2019
Publication date	Feb 25, 2025
Grant date	Feb 25, 2025

Abstract

Methods for preparing crystalline L-glufosinate ammonium monohydrate are disclosed. The methods include forming a mixture comprising water, a water-miscible organic solvent, ammonium hydroxide, and a glufosinate starting material containing L-glufosinate ammonium and D-glufosinate ammonium. L-Glufosinate ammonium monohydrate is crystallized and separated from the mixture, providing L-glufosinate ammonium monohydrate Form B. Compositions and methods employing the crystalline L-glufosinate ammonium monohydrate are also described.

First claim

What is claimed is:

1. A method for preparing crystalline L-glufosinate ammonium monohydrate, the method comprising:
(i) forming a mixture comprising a L-glufosinate starting material and an aqueous solution,
wherein the glufosinate starting material comprises L-glufosinate ammonium and D-glufosinate ammonium, and
wherein the aqueous solution comprises water and a water-miscible organic solvent;
(ii) crystallizing L-glufosinate ammonium from the mixture of step (i) to form L-glufosinate ammonium monohydrate crystals; and
(iii) separating at least a portion of the L-glufosinate ammonium monohydrate crystals from the aqueous solution following step (ii);
thereby preparing the crystalline L-glufosinate ammonium monohydrate,
wherein the crystalline L-glufosinate ammonium monohydrate comprises L-glufosinate ammonium monohydrate Form B.

2. The method of claim 1 , wherein the aqueous solution further comprises of an ammonia source.

3. The method of claim 2 , wherein the ammonia source is ammonium hydroxide.

4. The method of claim 1 , wherein the molar ratio of the L-glufosinate ammonium to the D-glufosinate ammonium in the glufosinate starting material is at least 70:30.

5. The method of claim 1 , wherein the molar ratio of the L-glufosinate ammonium to the D-glufosinate ammonium in the L-glufosinate starting material is at least 76:24.

6. The method of claim 1 , wherein the L-glufosinate starting material further comprises one or more components selected from the group consisting of L-glutamate and salts thereof, D-glutamate and salts thereof, L-pyroglutamate and salts thereof, 2-oxoglutarate and salts thereof, succinic acid and salts thereof, 2-oxo-4-(hydroxy(methyl)phosphinoyl)butyric acid and salts thereof, sodium sulfate, ammonium sulfate, sodium chloride, ammonium chloride, monosodium phosphate, disodium phosphate, monoammonium phosphate, and diammonium phosphate.

7. The method of claim 6 , wherein the L-glufosinate starting material comprises L-glutamate.

8. The method of claim 1 , wherein the amount of glufosinate in the L-glufosinate starting material ranges from about 70% (w/w) to about 90% (w/w).

9. The method of claim 8 , wherein the amount of glufosinate in the L-glufosinate starting material ranges from about 75% (w/w) to about 85% (w/w).

10. The method of claim 1 , wherein the water-miscible solvent is selected from the group consisting of methanol, ethanol, 1-propanol, 2-propanol, acetonitrile, tetrahydrofuran, 1,4-dioxane, 1-methyl-2-propanol, 1,2-propanediol, and 1,2-ethanediol.

11. The method of claim 10 , wherein the water-miscible organic solvent is methanol.

12. The method of claim 1 , wherein the ratio of the water-miscible organic solvent to the water in the aqueous solution ranges from about 45:55 to about 95:5 by volume.

13. The method of claim 1 , wherein the ratio of the water-miscible organic solvent to the water in the aqueous solution ranges from about 45:55 to about 65:35 by volume.

14. The method of claim 1 , wherein the concentration of ammonium hydroxide in the aqueous solution ranges from about 0.1M to about 1M.

15. The method of claim 14 , wherein the concentration of ammonium hydroxide in the aqueous solution is about 0.4 M.

16. The method of claim 1 , wherein the ratio of the L-glufosinate starting material to the aqueous solution in step (i) ranges from about 0.5:1 to about 5:1 by weight.

17. The method of claim 16 , wherein the ratio of the L-glufosinate starting material to the aqueous solution in step (i) ranges from about 1:1 to about 2:1 by weight.

18. The method of claim 1 , wherein step (ii) comprises heating the mixture of step (i) to form a heated mixture.

19. The method of claim 18 , wherein the mixture of step (i) is heated to at least around 45° C.

20. The method of claim 17 , wherein the heated mixture is maintained at a temperature of at least around 45° C. for a period of time ranging from about 10 minutes to about 6 hours prior to step (iii).

21. The method of claim 18 , further comprising cooling the heated mixture to form a cooled mixture prior to step (iii).

22. The method of claim 21 , wherein the heated mixture is cooled to a temperature around 30° C. or less.

23. The method of claim 1 , wherein step (ii) comprises adding glufosinate seed crystals to the mixture of step (i).

24. The method of claim 18 , comprising adding glufosinate seed crystals to the heated mixture of step (ii).

25. The method of claim 23 , wherein the glufosinate seed crystals comprise L-glufosinate ammonium monohydrate Form B.

26. The method of claim 23 , wherein the mixture comprising the glufosinate seed crystals is maintained at a temperature around 30° C. for a period of time ranging from about 1 hour to about 24 hours prior to step (iii).

27. The method of claim 23 , wherein the glufosinate seed crystals are added in an amount ranging from about 0.05% (w/w) to about 30% (w/w) based on the amount of glufosinate in the L-glufosinate starting material.

28. The method of claim 27 , wherein the glufosinate seed crystals are added in an amount ranging from about 0.1% (w/w) to about 0.5% (w/w) based on the amount of glufosinate in the L-glufosinate starting material.

29. The method of claim 1 , wherein separating at least a portion of the L-glufosinate crystals in step (iii) comprises filtering the mixture of step (ii), centrifuging the mixture of step (ii), or a combination thereof.

30. The method of claim 1 , further comprising one or more steps of (iv) washing the L-glufosinate ammonium monohydrate crystals; and (v) drying the L-glufosinate ammonium monohydrate crystals.

31. The method of claim 1 , wherein the crystalline L-glufosinate ammonium monohydrate further comprises D-glufosinate.

32. The method of claim 31 , wherein the molar ratio of L-glufosinate to D-glufosinate is at least 90:10.

33. The method of claim 31 , wherein the molar ratio of L-glufosinate to D-glufosinate is at least 95:5.

34. The method of claim 1 , wherein the L-glufosinate ammonium monohydrate Form B is characterized by an X-ray powder diffraction (XRPD) pattern comprises at least three peaks selected from 10.0, 11.4, 12.5, 16.5, 17.4, 18.1, 19.6, 20.0, 21.8, 22.9, 23.6, 24.0, 25.1, 25.5, 26.1, 26.3, 26.4, 27.9, 28.2, 28.4, 28.7, 29.2, 30.2, 30.9, 31.6, 31.7, 32.7, 33.0, 33.3, 34.3, 35.2, 36.7, 37.2, 37.4, 37.8, 38.3, 38.7, and 39.3°2θ, ±0.2°2θ, as determined on a diffractometer using Cu-Kα radiation.

35. The method of claim 1 , wherein the L-glufosinate ammonium monohydrate Form B is characterized by a differential scanning calorimetry (DSC) curve exhibiting an endotherm with an onset around 123° C.

Assignees

• Basf Se

Inventors

• Green Brian Michael
• Witek Rachel Melissa
• Pavlova Nadejda
• Oberholzer Matthew Richard

Classifications

• C12Y104/03003

  D-Amino-acid oxidase (1.4.3.3) · CPC title

• C12N9/0024

  D-Amino acid oxidase (1.4.3.3) · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C12N9/1096

  transferring nitrogenous groups (2.6) · CPC title

• C07F9/301 Primary

  Acyclic saturated acids which can have further substituents on alkyl · CPC title