Crystal of monovalent cation salt of 3-hydroxyisovaleric acid and process for producing the crystal

Patent metadata

Field	Value
Publication number	US-10647653-B2
Application number	US-201615777318-A
Country	US
Kind code	B2
Filing date	Nov 18, 2016
Priority date	Nov 19, 2015
Publication date	May 12, 2020
Grant date	May 12, 2020

Abstract

The present invention provides a crystal of a monovalent cation salt of 3-hydroxyisovaleric acid (hereinafter, referred to as HMB), which is excellent in solubility and easy to handle, and a process for producing the crystal. A crystal of a monovalent cation salt of HMB is precipitated in an aqueous HMB solution containing a monovalent cation-containing compound and having a pH of 4.0 to 9.0, and the crystal of a monovalent cation salt of HMB is thereafter collected from the aqueous solution.

First claim

The invention claimed is:

1. A crystal of a monovalent cation salt of 3-hydroxyisovaleric acid, wherein the monovalent cation salt is a sodium salt having a powder X-ray diffraction with crystal peaks at diffraction angles (2θ) of 8.4±0.2°, 6.6±0.2°, 19.7±0.2°, 13.3±0.2°, and 29.4±0.2°;
the monovalent cation salt is a sodium salt having a powder X-ray diffraction with crystal peaks at diffraction angles (2θ) of 6.7±0.2°, 13.3±0.2°, and 20.0±0.2°;
the monovalent cation salt is a potassium salt having a powder X-ray diffraction with crystal peaks at diffraction angles (2θ) of 9.0±0.2°, 27.1±0.2°, 23.8±0.2°, 16.1±0.2°, and 22.9±0.2°; or
the monovalent cation salt is an ammonium salt having a powder X-ray diffraction with crystal peaks at diffraction angles (2θ) of 19.9±0.2°, 21.1±0.2°, 29.9±0.2°, 17.3±0.2°, and 18.0±0.2°.

2. The crystal according to claim 1 , wherein the monovalent cation salt is a sodium salt having a powder X-ray diffraction with crystal peaks at diffraction angles (2θ) of 8.4±0.2°, 6.6±0.2°, 19.7±0.2°, 13.3±0.2°, and 29.4±0.2°.

3. The crystal according to claim 2 , wherein the crystal further has peaks at diffraction angles (2θ) of 35.1±0.2°, 17.3±0.2°, 24.5±0.2°, 17.8±0.2°, and 29.9±0.2°.

4. The crystal according to claim 3 , wherein the crystal further has peaks at diffraction angles (2θ) of 16.6±0.2°, 23.9±0.2°, 18.8±0.2°, 18.0±0.2°, and 25.3±0.2°.

5. The crystal according to claim 1 , wherein the monovalent cation salt is a sodium salt having a powder X-ray diffraction with crystal peaks at diffraction angles (2θ) of 6.7±0.2°, 13.3±0.2°, and 20.0±0.2°.

6. The crystal according to claim 5 , wherein the crystal further has peaks at diffraction angles (2θ) of 6.0±0.2°, 47.7±0.2°, 40.6±0.2°, 26.7±0.2°, and 12.0±0.2°.

7. The crystal according to claim 5 , wherein the crystal has approximately the following unit cell parameters when measured at about −180° C.: a=10.6679 Å; b=5.8862 Å; c=26.736 Å; α=90°; β=97.966°; γ=90°; V=1662.6 Å 3 ; and Z=8; the calculated density (D calc , gcm −3 ) is 1.407 gcm −3 ; and the space group is C2/c.

8. The crystal according to claim 1 , wherein the monovalent cation salt is a potassium salt having a powder X-ray diffraction with crystal peaks at diffraction angles (2θ) of 9.0±0.2°, 27.1±0.2°, 23.8±0.2°, 16.1±0.2°, and 22.9±0.2°.

9. The crystal according to claim 8 , wherein the crystal further has peaks at diffraction angles (2θ) of 30.7±0.2°, 8.1±0.2°, 6.4±0.2°, 32.1±0.2°, and 28.5±0.2°.

10. The crystal according to claim 9 , wherein the crystal further has peaks at diffraction angles (2θ) of 40.1±0.2°, 31.1±0.2°, 24.6±0.2°, 18.7±0.2°, and 34.4±0.2°.

11. The crystal according to claim 1 , wherein the monovalent cation salt is an ammonium salt having a powder X-ray diffraction with crystal peaks at diffraction angles (2θ) of 19.9±0.2°, 21.1±0.2°, 29.9±0.2°, 17.3±0.2°, and 18.0±0.2°.

12. The crystal according to claim 11 , wherein the crystal further has peaks at diffraction angles (2θ) of 25.6±0.2°, 8.6±0.2°, 18.2±0.2°, 39.6±0.2°, and 40.5±0.2°.

13. The crystal according to claim 12 , wherein the crystal further has peaks at diffraction angles (2θ) of 28.8±0.2°, 39.7±0.2°, 18.6±0.2°, 15.5±0.2°, and 14.3±0.2°.

14. A process for producing a crystal of a monovalent cation salt of 3-hydroxyisovaleric acid (HMB) of claim 1 , comprising a step of concentrating an aqueous HMB solution containing a monovalent cation-containing compound and having a pH of 4.0 to 10.0 under reduced pressure at 20 to 60° C. to precipitate a crystal of a monovalent cation salt of HMB in the aqueous solution, and a step of collecting the crystal of a monovalent cation salt of HMB from the aqueous solution, wherein the monovalent cation-containing compound is a sodium-containing compound, a potassium-containing compound, or an ammonium-containing compound.

15. A process for producing a crystal of a monovalent cation salt of 3-hydroxyisovaleric acid (HMB) of claim 1 , comprising a step of adding, as a seed crystal, a crystal of a monovalent cation salt of HMB to an aqueous HMB solution containing a monovalent cation-containing compound and having a pH of 4.0 to 10.0, a step of precipitating a crystal of a monovalent cation salt of HMB in the aqueous solution, and a step of collecting the crystal of a monovalent cation salt of HMB from the aqueous solution, wherein the monovalent cation-containing compound is a sodium-containing compound, a potassium-containing compound, or an ammonium-containing compound.

16. The process according to claim 15 , wherein the step of precipitating a monovalent cation salt of HMB is a step of adding or adding dropwise a solvent selected from the group consisting of nitrile and ketone to precipitate a crystal of a monovalent cation salt of HMB.

17. The process according to claim 16 , wherein the nitrile is acetonitrile and the ketone is a solvent selected from the group consisting of acetone, methyl ethyl ketone, methyl isobutyl ketone and diethyl ketone.

18. The process according to claim 11 , wherein the monovalent cation-containing compound is a sodium-containing compound.

19. The process according to claim 11 , wherein the monovalent cation-containing compound is a potassium-containing compound.

20. The process according to claim 11 , wherein the monovalent cation-containing compound is an ammonium-containing compound.

21. The process according to claim 15 , wherein the monovalent cation-containing compound is a sodium-containing compound.

22. The process according to claim 15 , wherein the monovalent cation-containing compound is a potassium-co taming compound.

23. The process according to claim 15 , wherein the monovalent cation-containing compound is an ammonium-containing compound.

Assignees

• Kyowa Hakko Bio Co Ltd
• Otsuka Pharma Factory Inc

Inventors

• Yokoi Tomoya
• Nagano Hiroshi
• Shimizu Takayuki

Classifications

• C07C51/43 Primary

  by change of the physical state, e.g. crystallisation · CPC title

• C07C59/01 Primary

  Saturated compounds having only one carboxyl group and containing hydroxy or O-metal groups · CPC title

• C30B7/105

  using ammonia as solvent, i.e. ammonothermal processes · CPC title

• C30B29/58

  Macromolecular compounds · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title