Innovative preparation and crystallization of iosimenol

Patent metadata

Field	Value
Publication number	US-10544089-B2
Application number	US-201615772710-A
Country	US
Kind code	B2
Filing date	Nov 2, 2016
Priority date	Nov 4, 2015
Publication date	Jan 28, 2020
Grant date	Jan 28, 2020

Abstract

The present invention generally relates to a process of preparing iosimenol and a process of preparing a crystal of iosimenol, as well as a crystal of iosimenol prepared by these processes.

First claim

The invention claimed is:

1. A crystal of iosimenol characterized by a powder x-ray diffraction pattern having four or more 2θ±0.2 peaks and selected from about 8.1°, 9.6°, 9.9°, 10.0°, 10.7°, 15.4°, 16.9°, 18.0°, 18.6°, 18.9°, 20.1°, 20.4°, 21.9°, 22.2°, 22.5°, 24.8°, 26.1°, 26.8°, 27.5°, 28.9°, 29.4°, 29.7°, 30.5°, 34.1° and 34.6°, wherein measurement of said crystal is at a temperature of about 293 K.

2. The crystal of iosimenol of claim 1 characterized by a powder x-ray diffraction pattern having four or more 2θ±0.2 peaks and selected from about 8.1°, 20.4°, 21.9°, 22.2°, 22.5°, 26.8° and 30.5°, wherein measurement of said crystal is at a temperature of about 293 K.

3. A crystal of iosimenol characterized by unit cell parameters at T=293K substantially equal to the following: a=21.8919(16) Å, b=9.8210(9) Å, c=20.0233(12) Å, α=90°, β=94.955(1°), γ=90°, volume 4289(6) Å 3 and a monoclinic P21/a space group.

4. A process for preparing iosimenol of formula:

comprising reacting CVI of formula:

with an alkylating agent introducing 2,3-dihydroxypropyl group in the presence of an inorganic base in a solvent comprising 2-methoxyethanol.

5. The process of claim 4 , wherein the alkylating agent introducing 2,3-dihydroxypropyl group is selected from the group consisting of 3-halo-1,2-propanediol and glycidol.

6. The process of claim 4 , wherein the alkylating agent introducing 2,3-dihydroxypropyl group is 3-halo-1,2-propanediol.

7. The process of claim 4 , wherein the inorganic base is selected from the group consisting of an alkali metal hydroxide and an alkaline earth metal hydroxide.

8. The process of claim 4 , wherein the inorganic base is lithium hydroxide, calcium hydroxide, sodium hydroxide, potassium hydroxide or mixture thereof.

9. The process of claim 4 , wherein the reaction to prepare iosimenol is done in the presence of a metal halide besides an inorganic base.

10. The process of claim 9 , wherein the metal halide is selected from the group consisting of CaCl 2 , ZnCl 2 and MgCl 2 .

11. A process for preparation of the crystalline iosimenol of claim 1 from a saturated or supersaturated solution of iosimenol, comprising:
Step 1: suspending deionized iosimenol in a solvent mixture comprising water and one or more organic solvents selected from the group consisting of C 1 -C 6 linear or branched alkanols, alkoxyalkanols, C 2 -C 8 aliphatic ethers, and C 4 -C 6 cyclic ethers,
Step 2: subjecting the mixture to heat and/or ultrasonic to completely dissolve the iosimenol in the mixture,
Step 3: continuing to subject the solution to the same or different heat and/or ultrasonic to deposit the crystalline ioseminol of claim 1 , and
Step 4: collecting the resulting crystalline ioseminol of claim 1 on a filter.

12. The process of claim 11 , wherein the heating in Step 2 and/or Step 3 is done with microwave.

13. The process of claim 11 , wherein the organic solvent in Step 1 is selected from the group consisting of methanol, ethanol, n-propanol, 2-propanol, n-butanol, butanol, sec-butanol, tert-butanol, pentanols including isoamylalcohols, hexanols and 2-methoxyethanol, 2-ethoxyethanol, 1-methoxy-2-propanol and 2-isopropoxyethanol.

14. The process of claim 11 , wherein the solvent mixture in Step 1 contains up to 20% water.

15. The process of claim 11 , wherein the crystallization process in Step 3 may be initiated by adding a seed of iosimenol crystal while or after the temperature is raised.

16. The process of claim 11 , wherein trometamol is used to buffer pH during crystallization process.

17. The process of claim 11 , wherein Steps 2 and 3 are done at 70° C.-140° C.

18. The process of claim 11 , wherein the concentration of iosimenol as the starting material in Step 1 is 10 w/v %-60 w/v %.

Assignees

• Otsuka Pharma Co Ltd

Inventors

• Malinak Jiri
• Hlavacek Ivan
• Prokop Jiri
• Masuda Yoshito

Classifications

• C07C231/12 Primary

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

• C07C237/46 Primary

  having carbon atoms of carboxamide groups, amino groups and at least three atoms of bromine or iodine, bound to carbon atoms of the same non-condensed six-membered aromatic ring · CPC title

• C07C231/24

  Separation; Purification · CPC title

• C07C231/08

  from amides by reaction at nitrogen atoms of carboxamide groups · CPC title

• B01D2009/0086

  Processes or apparatus therefor · CPC title