Method for crystallization of 2-amino-2-[2-[4-(3-benzyloxyphenylthio)-2-chlorophenyl]ethyl]-1,3-propanediol hydrochloride

Patent metadata

Field	Value
Publication number	US-9920005-B2
Application number	US-201615281942-A
Country	US
Kind code	B2
Filing date	Sep 30, 2016
Priority date	Mar 24, 2008
Publication date	Mar 20, 2018
Grant date	Mar 20, 2018

Abstract

A method for highly efficiently preparing high purity crystals of 2-amino-2-[2-[4-(3-benzyloxyphenylthio)-2-chloro-phenyl]-ethyl]-1,3-propanediol hydrochloride. The method involves dissolving 2-amino-2-[2-[4-(3-benzyloxyphenylthio)-2-chlorophenyl]ethyl]-1,3-propanediol in a mixed solvent comprising a solvent in which its hydrochloride is highly soluble and a solvent in which its hydrochloride is less soluble, to prepare a solution of 2-amino-2-[2-[4-(3-benzyloxyphenylthio)-2-chlorophenyl]ethyl]-1,3-propanediol; and then adding hydrochloric acid to the resulting solution with stirring, to crystallize the hydrochloride of 2-amino-2-[2-[4-(3-benzyloxyphenylthio)-2-chloro-phenyl]ethyl]-1,3-propanediol.

First claim

What is claimed is:

1. A method for crystallizing 2-amino-2-[2-[4-(3-benzyloxyphenylthio)-2-chlorophenyl]-ethyl]-1,3-propanediol hydrochloride, comprising:
dissolving 2-amino-2-[2-[4-(3-benzyloxyphenylthio)-2-chlorophenyl]-ethyl]-1,3-propanediol in ethanol with heating;
adding ethyl acetate to the ethanol containing the 2-amino-2-[2-[4-(3-benzyloxyphenylthio)-2-chlorophenyl]-ethyl]-1,3-propanediol, resulting in a first solution;
adding 1 to 12 mole/L of hydrochloric acid to the first solution at a temperature in a range of 50° C. to 90° C. while stirring, resulting a second solution; and
forming crystalline particles of 2-amino-2-[2-[4-(3-benzyloxyphenylthio)-2-chlorophenyl]-ethyl]-1,3-propanediol hydrochloride from the second solution at a temperature in a range of from 0° C. to 30° C. while stirring,
wherein an amount of a mixed solvent comprising the ethanol and the ethyl acetate ranges from 20 to 50 times a mass of the 2-amino-2-[2-[4-(3-benzyloxyphenylthio)-2-chlorophenyl]-ethyl]-1,3-propanediol.

2. The method of claim 1 , wherein the forming of the crystalline particles is carried out while stirring the second solution at a tip speed of not less than 50 m/min.

3. The method of claim 1 , wherein the adding of the hydrochloric acid is carried out at a temperature in a range of from 60° C. to 70° C.

4. The method of claim 1 , wherein the hydrochloric acid has a concentration ranging from 3 to 6 mole/L.

5. The method of claim 1 , wherein the forming of the crystalline particles is carried out while stirring the second solution at a temperature in a range of from 5° C. to 25° C.

6. The method of claim 2 , wherein the adding of the hydrochloric acid is carried out at a temperature in a range of from 60° C. to 70° C.

7. The method of claim 2 , wherein the hydrochloric acid has a concentration ranging from 3 to 6 mole/L.

8. The method of claim 2 , wherein the forming of the crystalline particles is carried out while stirring the second solution at a temperature in a range of from 5° C. to 25° C.

9. The method of claim 3 , wherein the hydrochloric acid has a concentration ranging from 3 to 6 mole/L.

10. The method of claim 3 , wherein the forming of the crystalline particles is carried out while stirring the second solution at a temperature in a range of from 5° C. to 25° C.

11. The method of claim 4 , wherein the forming of the crystalline particles is carried out while stirring the second solution at a temperature in a range of from 5° C. to 25° C.

12. The method of claim 6 , wherein the hydrochloric acid has a concentration ranging from 3 to 6 mole/L.

13. The method of claim 6 , wherein the forming of the crystalline particles is carried out while stirring the second solution at a temperature in a range of from 5° C. to 25° C.

14. The method of claim 7 , wherein the forming of the crystalline particles is carried out while stirring the second solution at a temperature in a range of from 5° C. to 25° C.

15. The method of claim 9 , wherein the forming of the crystalline particles is carried out while stirring the second solution at a temperature in a range of from 5° C. to 25° C.

16. The method of claim 12 , wherein the forming of the crystalline particles is carried out while stirring the second solution at a temperature in a range of from 5° C. to 25° C.

Assignees

• Kyorin Seiyaku Kk

Inventors

• Komatsu Hidetaka
• Satoh Hiroya

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P19/02

  for joint disorders, e.g. arthritis, arthrosis · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61K31/138

  Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine (atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377) · CPC title